Gut microbiota and neurodevelopement analysis

Author

Aline Davias

Published

November 29, 2023

Part 1: Data description

Outcomes

Table 1: Neurodeveloppement variables description
Variable labels Min Q1 Median Mean Q3 Max N W_statistic_shapiro p_value_shapiro
Child interne score at 2 years (CBCL) 0 3 6 6.9 9 29 417 0.9 <0.001
Child externe score at 2 years (CBCL) 1 9 12 13.2 17 37 416 1 <0.001
Child social awareness score at 3 years (SRS) 0 4 5 5.6 7 15 407 1 <0.001
Child social cognition score at 3 years (SRS) 0 3 5 5.2 7 15 407 1 <0.001
Child social communication score at 3 years (SRS) 0 5 8 8.6 11 39 407 0.9 <0.001
Child social motivation score at 3 years (SRS) 0 3 5 5.9 8 21 407 0.9 <0.001
Child restricted interests and repetitive behavior score at 3 years (SRS) 0 1 3 3.6 5 18 407 0.9 <0.001
Child SRS total score at 3 years (SRS) 4 20 26 28.9 36 100 407 0.9 <0.001
Child inhibition score at 3 years (BRIEF-P) 16 20 24 23.9 27 45 405 1 <0.001
Child shift score at 3 years (BRIEF-P) 10 11 13 13.3 15 28 414 0.9 <0.001
Child emotional control score at 3 years (BRIEF-P) 10 12 14 14.8 17 29 414 0.9 <0.001
Child working memory score at 3 years (BRIEF-P) 17 18 21 21.6 24 43 406 0.9 <0.001
Child plan/organization score at 3 years (BRIEF-P) 10 12 14 14.1 16 25 411 1 <0.001
Verbal comprehension score at 3 years (IQ test) 81 104 113 113.0 120 144 381 1 <0.001
Visuospatiale score at 3 years (IQ test) 82 100 106 107.6 115 135 382 1 1.537864e-03
Work memory score at 3 years (IQ test) 75 100 106 106.3 112 146 380 1 1.486267e-02
Total IQ score at 3 years 83 103 110 111.4 118 145 381 1 9.672147e-03
Figure 1: Spearman correlations between neurodeveloppment variables

CBCL Y2

Interne score Y2

Figure 2: Distribution of CBCL interne score Y2 (n = 417)

Outliers values of child interne score at 2 years variable (CBCL)
ident ch_cbclintscore_y2
27630 19
28199 19
15218 20
17764 20
25913 20
22672 21
23696 21
24222 22
16786 24
27316 25
15713 26
15804 29

Externe score Y2

Figure 3: Distribution of CBCL externe score Y2 (n = 416)

ident ch_cbclextscore_y2
19494 30
14567 32
16786 34
15218 35
16088 37

SRS Y3

Social awareness score Y3

Figure 4: Distribution of social awareness score Y3 (SRS, n = 407)

Outliers values of child social awareness score at 3 years (SRS) variable
ident ch_socawar_y3
14986 12
16088 12
17886 12
18868 12
21185 12
21519 12
23250 12
26318 12
22042 13
25823 13
15218 15

Social cognition score Y3

Figure 5: Distribution of social cognition score Y3 (SRS, n = 407)

Outliers values of child social cognition score at 3 years (SRS) variable
ident ch_soccog_y3
16318 14
16407 14
19029 14
26952 14
23663 15
24226 15
26318 15

Social communication score at 3 years

Figure 6: Distribution of social communication score at 3 years (SRS, n = 407)

Outliers values of child social communication score at 3 years (SRS) variable
ident ch_soccom_y3
17668 21
24226 21
19677 22
22042 22
23805 22
16093 24
23696 25
26952 27
15218 39

Social motivation score Y3

Figure 7: Distribution of social motivation score Y3 (SRS, n = 407)

Outliers values of child social motivation score at 3 years (SRS) variable
ident ch_socmot_y3
15218 16
19029 16
24476 16
17524 17
23603 17
23020 18
14276 19
26952 19
15804 21

Restricted interests and repetitive behavior score Y3

Figure 8: Distribution of restricted interests and repetitive behavior score Y3 (SRS, n = 407)

Outliers values of child restricted interests and repetitive behavior score at 3 years (SRS) variable
ident ch_RRB_y3
14856 12
16088 12
17764 12
26952 12
22167 13
15821 14
25409 15
15218 18

SRS total score at 3 years

Figure 9: Distribution of SRS total score at 3 years (SRS, n = 407)

Outliers values of child SRS total score at 3 years (SRS) variable
ident ch_SRStotal_y3
19677 62
23696 62
24226 65
16093 70
26952 80
15218 100

BRIEF-P Y3

Inhibition score Y3

Figure 10: Distribution of inhibition score Y3 (BRIEF-P, n = 405)

Outliers values of child inhibition score at 3 years (BRIEF-P) variable
ident ch_briefpinhibit_y3
19418 38
19426 39
24226 39
15821 40
18868 40
16021 43
15218 44
16088 45

Shift score Y3

Figure 11: Distribution of shift score Y3 (BRIEF-P, n = 414)

Outliers values of child shift score at 3 years (BRIEF-P) variable
ident ch_briefpshift_y3
27316 22
15741 23
15804 26
14276 28

Emotional control score Y3

Figure 12: Distribution of emotional control score Y3 (BRIEF-P, n = 414)

Outliers values of child emotional control score at 3 years (BRIEF-P) variable
ident ch_briefpemocontrol_y3
15741 25
22992 25
24222 25
16088 27
16021 28
19426 28
25409 28
15218 29

Working memory score Y3

Figure 13: Distribution of working memory score Y3 (BRIEF-P, n = 406)

Outliers values of child working memory score at 3 years (BRIEF-P) variable
ident ch_briefpworkmemo_y3
27309 34
19418 37
24226 41
16088 43

Plan/organization score Y3

Figure 14: Distribution of plan/organization score Y3 (BRIEF-P, n = 411)

Outliers values of child plan/organization score at 3 years (BRIEF-P) variable
ident ch_briefpplan_y3
16088 25

IQ Y3

Verbal comprehension score Y3

Figure 15: Distribution of verbal comprehension score Y3 (IQ, n = 381)

Verbal comprehension score Y3 variable doesn’t have any outliers.

Visuospatiale score Y3

Figure 16: Distribution of visuospatiale score Y3 (IQ, n = 382)

Visuospatiale score at 3 years (IQ test) doesn’t have any outliers.

Work memory score Y3

Figure 17: Distribution of work memory score Y3 (IQ, n = 380)

Outliers values of work memory score at 3 years (IQ test) variable
ident ch_work_memory_IQ_Y3
28226 75
25269 78
25784 78
24374 79
14856 80
17496 134
22857 134
27891 134
23769 146

Total IQ score Y3

Figure 18: Distribution of total IQ score Y3 (IQ, n = 381)

Outliers values of total IQ score at 3 years variable
ident ch_total_IQ_Y3
26097 145
28047 145

Predictors

Table 2: Gut microbiota variables description at one year
Variable labels Min Q1 Median Mean Q3 Max N W_statistic_shapiro p_value_shapiro
Specific richness diversity in 1Y child gut microbiota ASV based (seq. depth = 5 000) 18 64 81 83.2 99 184 350 1 1.429062e-03
Shannon diversity in 1Y child gut microbiota ASV based (seq. depth = 5 000) 0 2 3 2.6 3 4 350 1 <0.001
Faith diversity in 1Y child gut microbiota ASV based (seq. depth = 5 000) 86 266 311 314.5 362 560 350 1 6.345057e-01
One year child feces relative abundance of phylum Firmicutes 1 22 36 38.1 51 91 356 1 <0.001
One year child feces relative abundance of phylum Actinobacteria 0 11 26 30.0 48 98 356 0.9 <0.001
One year child feces relative abundance of phylum Bacteroidetes 0 3 10 17.4 28 80 356 0.9 <0.001
One year child feces relative abundance of phylum Proteobacteria 0 0 2 8.3 7 93 356 0.6 <0.001
One year child feces relative abundance of genus Bifidobacterium 0 10 25 29.0 46 98 356 0.9 <0.001
One year child feces relative abundance of genus Bacteroides 0 2 9 15.6 26 78 356 0.8 <0.001
One year child feces relative abundance of genus Blautia 0 1 4 8.2 11 68 356 0.8 <0.001
One year child feces relative abundance of genus Escherichia_Shigella 0 0 1 6.6 5 93 356 0.5 <0.001
Table 3: Gut microbiota variables description at one year (log transformed)
Variable labels Min Q1 Median Mean Q3 Max N
One year child feces relative abundance of phylum Firmicutes 0 3 4 3.5 4 5 356
One year child feces relative abundance of phylum Actinobacteria -4 2 3 2.9 4 5 356
One year child feces relative abundance of phylum Bacteroidetes -Inf 1 2 -Inf 3 4 356
One year child feces relative abundance of phylum Proteobacteria -Inf -1 0 -Inf 2 5 356
One year child feces relative abundance of genus Bifidobacterium -4 2 3 2.8 4 5 356
One year child feces relative abundance of genus Bacteroides -Inf 1 2 -Inf 3 4 356
One year child feces relative abundance of genus Blautia -Inf 0 1 -Inf 2 4 356
One year child feces relative abundance of genus Escherichia_Shigella -Inf -2 0 -Inf 2 5 356
Table 4: visualization of -inf values after log transformation
ident ch_feces_rel_p3_Y1_ln ch_feces_rel_p4_Y1_ln ch_feces_rel_g2_Y1_ln ch_feces_rel_g3_Y1_ln ch_feces_rel_g4_Y1_ln
14173 4.0013507 3.76118491 4.0013507 -Inf 3.7330816
14979 3.2473059 -1.70675905 -3.4295257 -Inf -1.9944411
16115 -1.8336282 -1.79791010 -2.0342989 -Inf -1.7979101
16199 3.9841257 2.41167366 3.9841257 -Inf 2.4087316
16815 -2.4944719 1.59987269 -Inf 2.94621274 1.5998727
17095 2.0352511 -0.03902244 1.5745307 3.10049773 -Inf
17537 -0.3474013 -2.62466859 -0.6787584 -Inf -2.6246686
17700 -3.0402275 3.69019375 -3.0402275 -Inf 3.6848061
17741 1.8447974 0.36339523 1.8441227 -Inf -0.6125006
18673 -3.8495800 -2.30913502 -3.8495800 -2.55029708 -Inf
20640 2.3160464 0.72944149 2.2843500 3.55481991 -Inf
21511 3.6167621 3.85946829 3.6167621 -Inf 3.8518964
21967 2.9506783 0.16107821 2.7535488 1.85055883 -Inf
22059 0.8230470 4.02241500 -Inf 0.79290287 0.7553010
22368 4.1303734 1.78002318 3.8239975 -Inf 1.0516510
22809 -Inf 2.11185197 -Inf 0.06626866 2.0967944
23076 4.0280313 3.05793567 4.0280313 -Inf 3.0174951
23271 -Inf 3.63094162 -Inf 0.97573630 3.6275579
23327 -1.6907665 -Inf -1.6907665 1.52446633 -Inf
23769 -Inf 3.97694943 -Inf -Inf 2.8884448
23933 1.3343488 1.29793974 1.3343488 -Inf 0.7797483
25166 -0.9454993 -0.67434655 -1.4187870 3.17872231 -Inf
25344 3.5488133 1.90877329 3.5488133 -Inf 1.9080366
25913 2.2533679 1.59834855 2.1940970 2.17730336 -Inf
26457 -0.5737519 -0.77346516 -0.5911436 3.40043617 -Inf
27344 3.7990176 -0.97953604 3.7961633 0.75406751 -Inf
27490 0.2535176 3.76993665 0.2535176 -Inf 3.7233742
Figure 19: Spearman correlations between gut microbiota variables (n=350)

Alpha diversity

Specific richness

Figure 20: Distribution of the specific richness Y1 (n=350)

Outliers values of Specific richness variable
ident ch_feces_SpecRich_5000_ASV_Y1
27075 154
24255 158
23901 184

Shannon diversity

Figure 21: Distribution of the Shannon diversity Y1 (n=350)

Outliers values of Shannon diversity variable
ident ch_feces_Shannon_5000_ASV_Y1
23330 0.3792690
28130 0.9867788
16115 1.0087967
24587 1.0558328
18553 1.0624003
22720 1.1855234
14173 1.2115941

Faith’s phylogenetic diversity

Figure 22: Distribution of the Faith’s phylogenetic diversity Y1 (n=350)

Outliers values of Faith's phylogenetic diversity variable
ident ch_feces_Faith_5000_ASV_Y1
23769 85.94050
23330 93.96517
22720 106.85055
18440 505.49615
24255 521.84691
23901 559.55928

Taxonomy

Phylum Firmicutes relative abundance Y1

Figure 23: Distribution of the relative abundance of phylum Firmicutes Y1 (n=356)

Phylum Firmicutes variable at one year doesn’t have any outliers.

Phylum Actinobacteria Y1

Figure 24: Distribution of the relative abundance of phylum Actinobacteria Y1 (n=356)

Phylum Actinobacteria variable at one year doesn’t have any outliers.

Phylum Bacteroidetes Y1

Figure 25: Distribution of the relative abundance of phylum Bacteroidetes Y1 (n=356)

Outliers values of phylum Bacteroidetes variable
ident ch_feces_rel_p3_Y1
22198 70.99179
16606 76.94366
16650 78.31132
24006 78.76686
14856 80.30181
Figure 26: Distribution of the relative abundance of ln(phylum Bacteroidetes) Y1 (n=356)

Outliers values of phylum Bacteroidetes variable (ln)
ident ch_feces_rel_p3_Y1_ln
22809 -Inf
23271 -Inf
23769 -Inf
16294 -4.843215
23663 -4.822537
19261 -4.776515
26766 -4.058314
28130 -3.990227
24359 -3.986871
25943 -3.902646
24226 -3.878053
18673 -3.849580
25673 -3.757706
15645 -3.562371
21955 -3.457762
22094 -3.436857
16782 -3.434826
18002 -3.417399
22857 -3.289927
16546 -3.252476
26760 -3.223505
17673 -3.041327
17700 -3.040228
22812 -2.922557
15422 -2.893700
22126 -2.655846
23848 -2.624384

Phylum Proteobacteria Y1

Figure 27: Distribution of the relative abundance of phylum Proteobacteria Y1 (n=356)

Outliers values of phylum Proteobacteria variable
ident ch_feces_rel_p4_Y1
22992 17.43845
16403 17.50454
20151 18.00766
16766 18.42998
15066 18.55562
21048 19.64709
20194 19.73358
22167 20.55545
23603 21.24552
23076 21.28358
26806 22.15355
25433 22.87679
16958 24.66083
27658 24.67874
15567 24.82301
27706 24.94526
15741 25.67847
21785 25.85059
25784 26.10054
27747 27.90090
18501 28.26770
15422 28.44487
26882 29.20354
19261 30.38588
23816 30.99024
17664 35.91379
25668 36.53393
22640 37.17140
23271 37.74834
21839 37.90993
16435 39.13336
17700 40.05261
14173 42.99935
27490 43.37732
22364 44.71383
23275 45.57840
21511 47.44012
25943 52.63795
23769 53.35403
27305 53.50392
22059 55.83579
26750 59.01700
27002 59.23331
17673 59.81226
27023 62.53976
27954 62.99872
15768 64.65962
20502 66.62831
26237 67.07950
20386 67.93516
27968 71.50482
28226 71.58796
28130 74.46033
23330 93.31640
Figure 28: Distribution of the relative abundance of ln(phylum Proteobacteria) Y1 (n=356)

Outliers values of phylum Proteobacteria variable (ln)
ident ch_feces_rel_p4_Y1_ln
23327 -Inf
17617 -5.459735
16682 -5.270843

Genus Bifidobacterium Y1

Figure 29: Distribution of the relative abundance of genus Bifidobacterium Y1 (n=356)

Genus Bifidobacterium variable at one year doesn’t have any outliers.

Genus Bacteroides Y1

Figure 30: Distribution of the relative abundance of genus Bacteroides Y1 (n=356)

Outliers values of genus Bacteroides variable
ident ch_feces_rel_g2_Y1
25773 63.55170
22198 64.72573
22772 65.80880
16606 68.58547
16650 74.61496
14856 77.49379
24006 77.75224
Figure 31: Distribution of the relative abundance of ln(genus Bacteroides) Y1 (n=356)

Outliers values of genus Bacteroides variable (ln)
ident ch_feces_rel_g2_Y1_ln
16815 -Inf
22059 -Inf
22809 -Inf
23271 -Inf
23769 -Inf
17365 -6.318373
19261 -5.469662
26318 -5.402362
23848 -5.263441
20194 -5.230699
16294 -4.843215
28130 -4.837525
23663 -4.822537
25501 -4.633932
24954 -4.556295
22620 -4.532277
16782 -4.351116
25943 -4.308111
26606 -4.245873
22640 -4.230137
22857 -4.078385
26766 -4.058314
24359 -3.986871
24226 -3.878053
18673 -3.849580
20110 -3.772958
25673 -3.757706
18002 -3.618069
15645 -3.562371
22094 -3.532167
21955 -3.457762

Genus Blautia Y1

Figure 32: Distribution of the relative abundance of genus Blautia Y1 (n=356)

Outliers values of genus Blautia variable
ident ch_feces_rel_g3_Y1
24359 26.88639
26606 26.94677
26743 27.03046
24862 27.17326
16766 27.40951
22757 29.04340
23603 29.09020
17617 29.59134
26457 29.97717
24995 30.53021
18664 30.65735
18509 32.11204
18199 32.12291
17524 32.23506
27058 32.59997
14177 32.92643
20640 34.98152
22118 35.07580
27526 35.50186
24917 35.57943
27854 35.87615
15186 36.93569
25281 40.66080
19367 40.80985
22812 44.02528
16546 67.83070
Figure 33: Distribution of the relative abundance of ln(genus Blautia) Y1 (n=356)

Outliers values of genus Blautia variable (ln)
ident ch_feces_rel_g3_Y1_ln
14173 -Inf
14979 -Inf
16115 -Inf
16199 -Inf
17537 -Inf
17700 -Inf
17741 -Inf
21511 -Inf
22368 -Inf
23076 -Inf
23769 -Inf
23933 -Inf
25344 -Inf
27490 -Inf
15567 -5.890539
22720 -5.783764
18780 -5.716732
25773 -5.658367
27309 -5.314486
18002 -5.122147
28199 -5.051393
25416 -5.044199
23330 -5.033766
25943 -5.001258
19995 -4.977469
19261 -4.371050
22126 -4.106679
21185 -3.815206
25784 -3.590991
27002 -3.150986
27023 -3.017249
20502 -2.973199

Genera Escherichia and Shigella Y1

Figure 34: Distribution of the relative abundance of genera Escherichia and Shigella Y1 (n=356)

Outliers values of genera Escherichia and Shigella variable
ident ch_feces_rel_g4_Y1
25416 13.58948
15960 13.58987
18509 13.60713
27309 13.64755
28119 15.39361
16766 17.23670
22992 17.36016
23769 17.96535
20151 17.97046
21048 18.25990
15066 18.55379
22167 20.25002
19261 20.41874
23076 20.44003
15567 21.39657
25433 21.92901
26806 22.15355
27658 22.91080
23816 23.85316
27706 24.08937
15422 24.20503
21785 25.49000
15741 25.50147
25784 26.09135
27747 27.68118
18501 28.26770
28226 29.34613
21839 33.41706
17664 35.40139
25668 35.83815
22640 36.12863
23271 37.62083
17700 39.83740
27490 41.40386
14173 41.80775
22364 43.11800
23275 45.21610
21511 47.08227
27305 49.40641
20386 50.88671
25943 52.23419
27002 57.71162
26750 58.92070
27954 61.96936
27023 62.53976
15768 64.28868
20502 66.38433
26237 67.04383
28130 74.45240
23330 93.25777
Figure 35: Distribution of the relative abundance of ln(genera Escherichia and Shigella) Y1 (n=356)

Outliers values of genera Escherichia and Shigella variable (ln)
ident ch_feces_rel_g4_Y1_ln
17095 -Inf
18673 -Inf
20640 -Inf
21967 -Inf
23327 -Inf
25166 -Inf
25913 -Inf
26457 -Inf
27344 -Inf

Covariates

Overview of the potential covariates

484 correspond a la taille d’échantillon total de SEPAGES.

356 correspond à la taille d’échantillon selon les données de microbiote disponibles.

Les effectifs finaux après prise en conmpte des données de neurodeveloppement varient selon la variable de neurodeveloppement et sont visibles dans le flowchart Part 3.

Table 5:

Overview of the potential covariates (distribution and missing data)

Characteristic Distribution Missing data Distribution Missing data
N = 4841 N = 4842 N = 3561 N = 3562
Child age at the CBCL 2 years evaluation 106.14 (105.14, 108.00) 67/484 (14%) 106.14 (105.14, 108.14) 20/356 (5.6%)
Child age at the IQ 3 years evaluation 160.3 (158.6, 163.1) 102/484 (21%) 160.3 (158.6, 163.1) 41/356 (12%)
Child age at the SRS 3 years evaluation 158.4 (156.1, 160.9) 65/484 (13%) 158.1 (155.9, 160.4) 15/356 (4.2%)
Birth weight (Kg) 3.28 (3.04, 3.56) 5/484 (1.0%) 3.28 (3.03, 3.58) 0/356 (0%)
Birth weight



    <3 Kg 99 (21%) 5/484 (1.0%) 74 (21%) 0/356 (0%)
    3-3.4 Kg 236 (49%) 5/484 (1.0%) 174 (49%) 0/356 (0%)
    ≥3.5 Kg 144 (30%) 5/484 (1.0%) 108 (30%) 0/356 (0%)
Birth length (cm) 50.00 (49.00, 51.50) 12/484 (2.5%) 50.00 (49.00, 51.50) 1/356 (0.3%)
Birth length



    <50 cm 170 (36%) 12/484 (2.5%) 130 (37%) 1/356 (0.3%)
    50-51 cm 195 (41%) 12/484 (2.5%) 141 (40%) 1/356 (0.3%)
    ≥52 cm 107 (23%) 12/484 (2.5%) 84 (24%) 1/356 (0.3%)
Weight at one year (Kg) 9.31 (8.71, 10.13) 68/484 (14%) 9.25 (8.71, 10.17) 5/356 (1.4%)
Weight at one year



    <8.5 Kg 72 (17%) 68/484 (14%) 61 (17%) 5/356 (1.4%)
    8.5-9.9 Kg 228 (55%) 68/484 (14%) 192 (55%) 5/356 (1.4%)
    ≥10 Kg 116 (28%) 68/484 (14%) 98 (28%) 5/356 (1.4%)
Length at one year (cm) 76.00 (74.00, 78.00) 80/484 (17%) 76.00 (74.00, 78.00) 13/356 (3.7%)
Length at one year



    <75 cm 144 (36%) 80/484 (17%) 125 (36%) 13/356 (3.7%)
    75-77.9 cm 150 (37%) 80/484 (17%) 124 (36%) 13/356 (3.7%)
    ≥78 cm 110 (27%) 80/484 (17%) 94 (27%) 13/356 (3.7%)
Weight at 3 years (Kg) 14.45 (13.50, 15.55) 101/484 (21%) 14.38 (13.50, 15.55) 40/356 (11%)
Weight at 3 years



    9-13 Kg 126 (33%) 101/484 (21%) 105 (33%) 40/356 (11%)
    14 Kg 129 (34%) 101/484 (21%) 107 (34%) 40/356 (11%)
    15-20 Kg 128 (33%) 101/484 (21%) 104 (33%) 40/356 (11%)
Length at 3 years (cm) 95.0 (93.0, 97.3) 103/484 (21%) 95.3 (93.0, 97.4) 42/356 (12%)
Length at 3 years



    81-93 cm 123 (32%) 103/484 (21%) 96 (31%) 42/356 (12%)
    94-95 cm 129 (34%) 103/484 (21%) 110 (35%) 42/356 (12%)
    96-106 cm 129 (34%) 103/484 (21%) 108 (34%) 42/356 (12%)
Child sex



    Male 256 (53%) 5/484 (1.0%) 190 (53%) 0/356 (0%)
    Female 223 (47%) 5/484 (1.0%) 166 (47%) 0/356 (0%)
Maternal education



    ≥5 years after graduation 272 (56%) 2/484 (0.4%) 201 (57%) 2/356 (0.6%)
    3-4 years after graduation 127 (26%) 2/484 (0.4%) 97 (27%) 2/356 (0.6%)
    2 years or less after graduation 83 (17%) 2/484 (0.4%) 56 (16%) 2/356 (0.6%)
Maternal education



    ≥5 years after graduation 272 (56%) 2/484 (0.4%) 201 (57%) 2/356 (0.6%)
    <5 years after graduation 210 (44%) 2/484 (0.4%) 153 (43%) 2/356 (0.6%)
Maternal age at conception (years) 32.1 (29.9, 35.2) 0/484 (0%) 32.3 (29.9, 35.2) 0/356 (0%)
Maternal age at conception



    20-30 years 161 (33%) 0/484 (0%) 115 (32%) 0/356 (0%)
    31-33 years 161 (33%) 0/484 (0%) 119 (33%) 0/356 (0%)
    34-44 years 162 (33%) 0/484 (0%) 122 (34%) 0/356 (0%)
Woman living in couple during pregnancy 479 (99%) 0/484 (0%) 353 (99%) 0/356 (0%)
Maternal BMI before pregnancy (kg/m2) 21.5 (19.8, 23.9) 4/484 (0.8%) 21.5 (19.7, 23.7) 1/356 (0.3%)
Maternal BMI before pregnancy



    <19 Kg/m2 60 (13%) 4/484 (0.8%) 48 (14%) 1/356 (0.3%)
    19-23.9 Kg/m2 301 (63%) 4/484 (0.8%) 223 (63%) 1/356 (0.3%)
    ≥24 Kg/m2 119 (25%) 4/484 (0.8%) 84 (24%) 1/356 (0.3%)
Maternal parity



    0 222 (46%) 0/484 (0%) 164 (46%) 0/356 (0%)
    1 214 (44%) 0/484 (0%) 156 (44%) 0/356 (0%)
    2 48 (9.9%) 0/484 (0%) 36 (10%) 0/356 (0%)
Maternal parity



    None 222 (46%) 0/484 (0%) 164 (46%) 0/356 (0%)
    1 child or more 262 (54%) 0/484 (0%) 192 (54%) 0/356 (0%)
Breastfeeding duration (weeks) 26 (13, 43) 43/484 (8.9%) 26 (16, 43) 9/356 (2.5%)
Breastfeeding duration



    Not breastfed 40 (9.1%) 43/484 (8.9%) 29 (8.4%) 9/356 (2.5%)
    <24 weeks 157 (36%) 43/484 (8.9%) 122 (35%) 9/356 (2.5%)
    24-47 weeks 149 (34%) 43/484 (8.9%) 117 (34%) 9/356 (2.5%)
    Still breastfeed at 48 weeks 95 (22%) 43/484 (8.9%) 79 (23%) 9/356 (2.5%)
Gestational duration, completed weeks 40.00 (39.00, 40.00) 4/484 (0.8%) 40.00 (39.00, 40.00) 0/356 (0%)
Delivery mode



    Vaginal delivery 398 (83%) 5/484 (1.0%) 298 (84%) 0/356 (0%)
    C-section 81 (17%) 5/484 (1.0%) 58 (16%) 0/356 (0%)
Period of introduction of solid food 0-12 months old



    Between 0 and 6 months old 293 (77%) 105/484 (22%) 253 (79%) 37/356 (10%)
    Between 6 and 12 months old 66 (17%) 105/484 (22%) 50 (16%) 37/356 (10%)
    Not introduced at 12 months old 20 (5.3%) 105/484 (22%) 16 (5.0%) 37/356 (10%)
Presence of pets



    No 271 (70%) 98/484 (20%) 222 (71%) 45/356 (13%)
    One or more 115 (30%) 98/484 (20%) 89 (29%) 45/356 (13%)
Antibiotics use between 0-12 months old



    No 332 (72%) 23/484 (4.8%) 246 (69%) 1/356 (0.3%)
    Yes 129 (28%) 23/484 (4.8%) 109 (31%) 1/356 (0.3%)
Learning materials score at 3 years of age (HOME questionnaire) 8.00 (7.00, 9.00) 107/484 (22%) 8.00 (7.00, 9.00) 43/356 (12%)
Language stimulation score at 3 years of age (HOME questionnaire) 6.00 (5.00, 7.00) 107/484 (22%) 6.00 (6.00, 7.00) 43/356 (12%)
Academic stimulation score at 3 years of age (HOME questionnaire) 3.00 (3.00, 4.00) 107/484 (22%) 3.00 (3.00, 4.00) 43/356 (12%)
Variety score at 3 years of age (HOME questionnaire) 7.00 (7.00, 8.00) 107/484 (22%) 7.00 (7.00, 8.00) 43/356 (12%)
HOME questionnaire total score 25.00 (23.00, 26.00) 107/484 (22%) 25.00 (23.00, 26.00) 43/356 (12%)
Maternal anxiety score during the third trimester of pregnancy 6.0 (4.0, 8.0) 44/484 (9.1%) 6.00 (4.00, 8.00) 12/356 (3.4%)
Maternal depression score during the third trimester of pregnancy 4.00 (2.00, 5.00) 45/484 (9.3%) 4.00 (2.00, 5.00) 13/356 (3.7%)
Maternal anxiety and depression score during the third trimester of pregnancy 10.0 (7.0, 13.0) 46/484 (9.5%) 10.0 (7.0, 13.0) 14/356 (3.9%)
Maternal anxiety score when child is one year old 7.0 (5.0, 9.0) 167/484 (35%) 7.0 (5.0, 9.0) 81/356 (23%)
Maternal depression score when child is one year old 3.00 (2.00, 6.00) 167/484 (35%) 3.00 (2.00, 6.00) 81/356 (23%)
Maternal anxiety and depression score when child is one year old 10.0 (8.0, 14.0) 167/484 (35%) 11.0 (8.0, 14.0) 81/356 (23%)
Maternal active smoking during pregnancy



    No 401 (93%) 54/484 (11%) 310 (94%) 26/356 (7.3%)
    Yes 29 (6.7%) 54/484 (11%) 20 (6.1%) 26/356 (7.3%)
Maternal passive smoking during pregnancy



    No 352 (80%) 44/484 (9.1%) 277 (82%) 17/356 (4.8%)
    Yes 88 (20%) 44/484 (9.1%) 62 (18%) 17/356 (4.8%)
Child passive smoking during the first year of life



    No 340 (78%) 50/484 (10%) 277 (78%) 0/356 (0%)
    Yes 94 (22%) 50/484 (10%) 79 (22%) 0/356 (0%)
Child perinatal exposure to tabacco up to one year



    No 267 (63%) 63/484 (13%) 224 (66%) 16/356 (4.5%)
    Yes 154 (37%) 63/484 (13%) 116 (34%) 16/356 (4.5%)
Child perinatal passive smoking up to one year



    No 277 (65%) 61/484 (13%) 232 (67%) 12/356 (3.4%)
    Yes 146 (35%) 61/484 (13%) 112 (33%) 12/356 (3.4%)
Maternal alcohol consumption during pregnancy



    Did not drink 149 (32%) 23/484 (4.8%) 110 (31%) 4/356 (1.1%)
    Drank only before finding out she was pregnant 208 (45%) 23/484 (4.8%) 168 (48%) 4/356 (1.1%)
    Drank 104 (23%) 23/484 (4.8%) 74 (21%) 4/356 (1.1%)
Maternal alcohol consumption during pregnancy



    Did not drink 149 (32%) 23/484 (4.8%) 110 (31%) 4/356 (1.1%)
    Drank only before finding out she was pregnant 208 (45%) 23/484 (4.8%) 168 (48%) 4/356 (1.1%)
    <1drink/month when she knew she was pregnant 81 (18%) 23/484 (4.8%) 63 (18%) 4/356 (1.1%)
    >1drink/month when she knew she was pregnant 23 (5.0%) 23/484 (4.8%) 11 (3.1%) 4/356 (1.1%)
Main mode of child care at 6 months (2 categories, optimized 2)



    Collective day care 253 (63%) 81/484 (17%) 209 (63%) 25/356 (7.0%)
    Other 150 (37%) 81/484 (17%) 122 (37%) 25/356 (7.0%)
Main mode of child care at 12 months (2 categories, optimized 2)



    Collective day care 326 (81%) 81/484 (17%) 271 (82%) 25/356 (7.0%)
    Other 77 (19%) 81/484 (17%) 60 (18%) 25/356 (7.0%)
Main mode of child care up to 1 year



    Collective day care 334 (83%) 81/484 (17%) 278 (84%) 25/356 (7.0%)
    Other 69 (17%) 81/484 (17%) 53 (16%) 25/356 (7.0%)
Main mode of child care at 6 months (3 categories, optimized 2)



    Collective day care 81 (20%) 81/484 (17%) 61 (18%) 25/356 (7.0%)
    Nursery assistant (out child home) 172 (43%) 81/484 (17%) 148 (45%) 25/356 (7.0%)
    Other 150 (37%) 81/484 (17%) 122 (37%) 25/356 (7.0%)
Main mode of child care at 12 months (3 categories, optimized 2)



    Collective day care 132 (33%) 81/484 (17%) 101 (31%) 25/356 (7.0%)
    Nursery assistant (out child home) 194 (48%) 81/484 (17%) 170 (51%) 25/356 (7.0%)
    Other 77 (19%) 81/484 (17%) 60 (18%) 25/356 (7.0%)
Main mode of child care up to 1 year



    Collective day care 135 (33%) 81/484 (17%) 104 (31%) 25/356 (7.0%)
    Nursery assistant (out child home) 199 (49%) 81/484 (17%) 174 (53%) 25/356 (7.0%)
    Other 69 (17%) 81/484 (17%) 53 (16%) 25/356 (7.0%)
Paternal ethinicity



    Caucassian 390 (95%) 74/484 (15%) 304 (95%) 35/356 (9.8%)
    Others 20 (4.9%) 74/484 (15%) 17 (5.3%) 35/356 (9.8%)
Paternal education



    ≥5 years after graduation 189 (64%) 190/484 (39%) 157 (64%) 110/356 (31%)
    3-4 years after graduation 49 (17%) 190/484 (39%) 41 (17%) 110/356 (31%)
    2 years or less after graduation 56 (19%) 190/484 (39%) 48 (20%) 110/356 (31%)
Paternal age at child birth (years) 34.4 (31.6, 38.0) 82/484 (17%) 34.4 (31.6, 37.9) 39/356 (11%)
Paternal age at child birth



    23-31 years 134 (33%) 82/484 (17%) 106 (33%) 39/356 (11%)
    32-36 years 134 (33%) 82/484 (17%) 106 (33%) 39/356 (11%)
    37-72 years 134 (33%) 82/484 (17%) 105 (33%) 39/356 (11%)
Maternal ethnicity



    Caucassian 445 (96%) 21/484 (4.3%) 341 (97%) 3/356 (0.8%)
    Others 18 (3.9%) 21/484 (4.3%) 12 (3.4%) 3/356 (0.8%)
Child age at stool collection (weeks) 53.6 (52.2, 55.4) 131/484 (27%) 53.5 (52.2, 55.4) 7/356 (2.0%)
MiSeq analytic batch effect



    R2 218 (61%) 128/484 (26%) 218 (61%) 0/356 (0%)
    R3 138 (39%) 128/484 (26%) 138 (39%) 0/356 (0%)
1 Median (IQR); n (%)
2 N missing/No. obs. (% missing); N missing/No. obs. (% missing)

Continuous covariates

Table 6: Description of the continuous covariates
Variable labels Min Q1 Median Mean Q3 Max N W_statistic_shapiro p_value_shapiro
Child age at the CBCL 2 years evaluation 100 105 106 106.7 108 121 417 0.9 <0.001
Child age at the IQ 3 years evaluation 144 159 160 161.3 163 184 382 0.9 <0.001
Child age at the SRS 3 years evaluation 144 156 158 159.0 161 198 419 0.9 <0.001
Birth weight (Kg) 1 3 3 3.3 4 5 479 1 <0.001
Birth length (cm) 36 49 50 50.1 52 59 472 0.9 <0.001
Weight at one year (Kg) 6 9 9 9.4 10 13 416 1 <0.001
Length at one year (cm) 68 74 76 76.0 78 84 404 1 2.069817e-01
Weight at 3 years (Kg) 9 14 14 14.6 16 20 383 1 7.891381e-03
Length at 3 years (cm) 81 93 95 95.2 97 106 381 1 6.023938e-02
Maternal age at conception (years) 21 30 32 32.5 35 45 484 1 6.554413e-02
Maternal BMI before pregnancy (kg/m2) 17 20 22 22.4 24 42 480 0.8 <0.001
Breastfeeding duration (weeks) 0 13 26 26.6 43 48 441 0.9 <0.001
Gestational duration, completed weeks 28 39 40 39.2 40 42 480 0.8 <0.001
Learning materials score at 3 years of age (HOME questionnaire) 4 7 8 8.0 9 11 377 0.9 <0.001
Language stimulation score at 3 years of age (HOME questionnaire) 2 5 6 6.0 7 7 377 0.8 <0.001
Academic stimulation score at 3 years of age (HOME questionnaire) 0 3 3 3.3 4 5 377 0.9 <0.001
Variety score at 3 years of age (HOME questionnaire) 4 7 7 7.3 8 11 377 0.9 <0.001
HOME questionnaire total score 16 23 25 24.5 26 32 377 1 <0.001
Maternal anxiety score during the third trimester of pregnancy 0 4 6 6.4 8 18 440 1 <0.001
Maternal depression score during the third trimester of pregnancy 0 2 4 4.2 5 19 439 0.9 <0.001
Maternal anxiety and depression score during the third trimester of pregnancy 2 7 10 10.6 13 37 438 0.9 <0.001
Maternal anxiety score when child is one year old 1 5 7 7.2 9 17 317 1 <0.001
Maternal depression score when child is one year old 0 2 3 3.9 6 14 317 0.9 <0.001
Maternal anxiety and depression score when child is one year old 2 8 10 11.1 14 31 317 1 <0.001
Paternal age at child birth (years) 24 32 34 35.2 38 73 402 0.9 <0.001
Child age at stool collection (weeks) 48 52 54 54.2 55 70 353 0.9 <0.001
Figure 36: Spearman correlations between continuous covariates

Child age at the CBCL 2 years evaluation

Figure 37: Distribution of child age at the CBCL 2 years evaluation (n = 417/484)

Outliers values of child age at CBCL 2 years test variable
ident ch_age_CBCL_Y2
24246 99.85714
14638 112.42857
18673 112.57143
18501 112.71429
20306 113.00000
25784 113.00000
21511 113.14286
26457 113.28571
21112 113.85714
14461 114.00000
23994 114.00000
19954 115.14286
25409 115.42857
24298 116.00000
27015 116.71429
23250 117.85714
23258 120.71429

Child age at the IQ 3 years evaluation

Figure 38: Distribution of child age at the IQ 3 years evaluation (n = 382/484)

Outliers values of child age at IQ 3 years test variable
ident ch_age_IQ_Y3
17465 143.5714
16650 170.0000
25344 170.1429
25572 170.7143
25773 170.8571
14177 171.2857
26136 171.5714
14184 171.7143
27943 171.7143
27866 172.4286
22620 173.0000
15960 173.4286
14013 173.7143
25784 175.0000
26882 180.2857
17115 183.7143

Child age at the SRS and BRIEF-P 3 years evaluation

Figure 39: Distribution of child age at the SRS and BRIEF-P 3 years evaluation (n = 419/484)

Outliers values of child age at SRS and BRIEF-P 3 years variable
ident ch_age_SRS_BRIEFP_Y3
17465 143.5714
27084 168.2857
28021 168.7143
26806 169.4286
15704 169.8571
17906 169.8571
22672 170.4286
23696 171.4286
27943 172.2857
22620 173.0000
14013 173.7143
23994 176.0000
21271 176.4286
14638 178.4286
26882 197.5714

Paternal age at child birth (years)

Figure 40: Distribution of paternal age at child birth (years) (n = 402/484)

Outliers values of paternal age at child birth variable
ident fa_age
20905 48.84110
26539 49.09863
26882 50.93425
18086 55.10137
14886 57.95068
22620 72.57808

Maternal age at conception (years)

Figure 41: Distribution of maternal age at conception (years) (n = 484/484)

Outliers values of maternal age during pregnancy variable
ident mo_age
15370 20.56400
15929 44.87337
22620 45.32512
20905 45.47023

Maternal BMI before pregnancy (kg/m2)

Figure 42: Distribution of maternal BMI before pregnancy (kg/m2) (n = 480/484)

Outliers values of maternal BMI before pregnancy variable
ident mo_bmi_bepr
25668 30.33111
15066 30.39341
18700 30.48316
16088 30.58181
27871 31.08530
18673 31.13306
16093 31.67393
14934 31.78093
26871 31.93935
19216 33.05785
17585 34.18245
23475 35.11111
24897 35.93750
23327 36.71875
25806 38.66746
16782 40.25726
22042 41.27022
18721 41.83683
27442 41.95202

Maternal anxiety score during the third trimester of pregnancy

Figure 43: Distribution of maternal anxiety score during the third trimester of pregnancy (n = 440/484)

Outliers values of maternal anxiety score T3 variable
ident mo_hadanxscore_grt3_imp
14433 15
14732 15
15034 15
18873 15
25166 15
17717 16
16294 17
19125 17
16088 18

Maternal depression score during the third trimester of pregnancy

Figure 44: Distribution of maternal depression score during the third trimester of pregnancy (years) (n = 439/484)

Outliers values of maternal depression score T3 variable
ident mo_haddepscore_grt3_imp
14184 10
14680 10
15326 10
15713 10
16786 10
18721 10
19971 10
20536 10
20905 10
23020 10
23250 10
25409 10
25668 10
27539 10
14276 11
14930 11
18199 11
23475 11
23974 11
17248 12
22042 12
14433 13
23076 13
23306 14
27305 14
16294 18
16088 19

Maternal anxiety and depression score during the third trimester of pregnancy

Figure 45: Distribution of maternal anxiety and depression score during the third trimester of pregnancy (n = 438/484)

Outliers values of maternal anxiety and depression score T3 variable
ident mo_hadtotscore_grt3_imp
15034 23
18873 23
19125 23
20536 23
23306 23
14732 24
23076 25
23475 25
14433 28
16294 35
16088 37

Maternal anxiety score when child is one year old

Figure 46: Distribution of maternal anxiety score when child is one year old (n = 317/484)

Outliers values of maternal anxiety score at 1 year variable
ident mo_hadanxscore_y1_imp
15645 16
17906 16
17764 17
19764 17
23603 17

Maternal depression score when child is one year old

Figure 47: Distribution of maternal depression score when child is one year old(n = 317/484)

Outliers values of maternal depression score at 1 year variable
ident mo_haddepscore_y1_imp
27316 13
14732 14
17764 14
28047 14

Maternal anxiety and depression score when child is one year old

Figure 48: Distribution of maternal anxiety and depression score when child is one year old (n = 317/484)

Outliers values of maternal anxiety and depression score at 1 year variable
ident mo_hadtotscore_y1_imp
24359 24
14732 25
23603 25
28119 25
17906 26
17764 31

Breastfeeding duration (weeks)

Figure 49: Distribution of breastfeeding duration (weeks) (n = 441/484)

Breastfeeding duration variable doesn’t have outliers.

Gestational duration (completed weeks)

Figure 50: Distribution of gestational duration (completed weeks) (n = 480/484)

Outliers values of gestational age variable
ident po_gd
14886 28
17827 30
15929 32
16815 33
25668 33
25943 33
14880 34
23901 35
26136 35
26760 35
27666 35
14548 36
15075 36
15821 36
15921 36
18186 36
18780 36
20536 36
22620 36
23076 36
23306 36
24829 36
25565 36
26891 36
14412 37
14433 37
14461 37
15239 37
15836 37
16021 37
16490 37
16546 37
17248 37
18553 37
18700 37
19125 37
19339 37
20110 37
21271 37
21519 37
22772 37
22812 37
23610 37
23957 37
25337 37
25509 37
25806 37
26168 37
26237 37
27442 37
27650 37
28130 37
27490 42

Child age at stool collection (weeks)

Figure 51: Distribution of child age at stool collection (weeks) (n = 353/484)

Outliers values of child at at stool collection variable
ident ch_feces_age_w_Y1
28021 60.19048
27201 60.40476
27442 60.79563
16407 60.79762
27526 61.07887
20640 61.36756
24587 61.62202
15186 62.08482
26136 62.19345
27943 62.22272
14638 62.91518
21271 62.93651
14680 63.65575
14567 64.52827
17958 65.24058
22118 65.48760
27866 65.66925
27871 67.57143
15487 68.40377
26882 69.83284
21148 70.37063

Learning materials score at 3 years of age (HOME questionnaire)

Figure 52: Distribution of learning materials score at 3 years of age (n = 377/484)

Learning materials score at 3 years of age (HOME questionnaire) variable doesn’t have outliers.

Language stimulation score at 3 years of age (HOME questionnaire)

Figure 53: Distribution of language stimulation score at 3 years of age (n = 377/484)

Language stimulation score at 3 years of age (HOME questionnaire) variable doesn’t have outliers.

Academic stimulation score at 3 years of age (HOME questionnaire)

Figure 54: Distribution of academic stimulation score at 3 years of age (n = 377/484)

Outliers values of home_academic_y3 variable
ident home_academic_y3
14567 0
14895 0
15171 0
18868 0
14576 1
14856 1
14958 1
15186 1
15218 1
16782 1
17138 1
23306 1
24335 1
28066 1

Variety score at 3 years of age (HOME questionnaire)

Figure 55: Distribution of variety score at 3 years of age (n = 377/484)

Outliers values of home_variety_y3 variable
ident home_variety_y3
15813 4
16546 4
27658 4
14930 5
15034 5
15186 5
15218 5
15367 5
16435 5
16766 5
17095 5
17668 5
17708 5
18581 5
19677 5
22198 5
22388 5
25043 5
25409 5
25509 5
26237 5
27567 5
27747 5
27915 5
14557 11

HOME questionnaire total score

Figure 56: Distribution of HOME questionnaire total score (n = 377/484)

Outliers values of home_total_y3 variable
ident home_total_y3
15171 16
15186 17
18868 17
15218 18
15813 18
16546 18
22957 31
25337 31
26760 31
19387 32

Birth weight (Kg)

Figure 57: Distribution of birth weight (Kg) (n = 479/484)

Outliers values of child weight at birth variable
ident po_w_kg
17827 0.995
14886 1.015
15929 1.880
23076 1.880
19587 2.070
14412 2.160
24829 2.170
26760 2.190
25565 2.200
24485 4.480
19418 4.520
27058 4.590
23371 4.670

Birth length (cm)

Figure 58: Distribution of birth length (cm) (n = 472/484)

Outliers values of child length at birth variable
ident po_he
17827 36.4
14886 38.0
15929 42.5
23076 42.5
26760 43.0
14880 44.0
24829 44.0
14412 45.0
16179 45.0
16815 45.0
16958 55.5
19261 56.0
19708 56.0
14476 57.0
17708 57.5
23924 58.5

Weight at one year (Kg)

Figure 59: Distribution of weight at one year (Kg) (n = 416/484)

Outliers values of child weight at one year variable
ident ch_w_Y1
24829 6.0175
22388 12.8850
18721 13.3850

Length at one year (cm)

Figure 60: Distribution of length at one year (cm) (n = 404/484)

Outliers values of child length at one year variable
ident ch_he_Y1
24829 67.75

Weight at 3 years (Kg)

Figure 61: Distribution of weight at 3 years (Kg) (n = 383/484)

Outliers values of child weight at 3 years variable
ident ch_w_Y3
24829 9.15
16088 18.65
22223 18.65
22388 18.75
20098 19.30
22288 19.35
17617 19.50

Length at 3 years (cm)

Les enfants avec les ident “27309”, “17668” et “17958” ont été passé en données manquantes car les valeurs taille à 3 ans étaient improbables (environ égales à 10 cm)

Figure 62: Distribution of length at 3 years (cm) (n = 381/484)

Outliers values of child length at 3 years variable
ident ch_he_Y3
24829 81.00
25913 86.00
16179 86.25
26117 86.25
20194 86.50
22388 104.00
24127 104.00
25915 104.25
22288 105.00
20151 105.50
28021 106.00

Part 2: Choice of covariates and their coding

Directed acyclic graph

Figure 63: Directed acyclic graph

Ici on teste :

  • toutes les covariables potentielles identifiées avec le DAG (Univariates models)
  • 1 modèle multivarié en modèle univarié toutes les covariables potentielles (Multivariate model test 1, avant inclusion des variables d’intérêt) :
    • les covariables de ce modèles sont :
      • var_age (âge de l’enfant lors du test de neurodeveloppement)
      • po_w_kg_3cat (poids de l’enfant à la naissance
      • po_he_3cat (taille de l’enfant à la naissance
      • mo_dipl_2cat (niveau de diplome de la mère)
      • mo_age (âge maternel)
      • mo_bmi_bepr_3cat (IMC maternel avant la grossesse)
      • ch_sex (sexe de l’enfant)
      • mo_par_2cat (parité)
      • ch_bf_duration_till48w_4cat (durée de la l’allaitement)
      • po_gd (durée de la gestation)
      • po_delmod (mode d’accouchement
      • ch_food_intro_Y1_3cat (période d’introduction de la nourriture solide)
      • mo_pets (présence d’animaux)
      • ch_antibio_Y1_2cat (prise d’antibiotique entre la naissance et l’âge de 1 an)
      • home_total_y3 (score HOME à 3 ans)
      • mo_hadtotscore_grt3_imp (score d’anxiété et de dépression de la mère lors du 3ème trimestre de la grossesse)
      • mo_tob_gr_anyt_yn_n2 (tabagisme actif de la mère pendant la grossesse)
      • ch_tabacco_passive_up_to_Y1 (tabagisme périnatal passif de l’enfant (tabagisme passif de la mère pendant la grossesse + tabagisme passif de l’enfant de la naissance à l’âge de 1 an)
      • ch_care_main_12m_opt2_2c (mode de garde principal de l’enfant à l’âge de 1 an)
    • La différence avec le deuxième modèle multivarié porte sur la variable mode de garde
  • 1 modèle multivarié en modèle univarié toutes les covariables potentielles (Multivariate model test 1, avant inclusion des variables d’intérêt) :
    • les covariables de ce modèles sont :
      • var_age (âge de l’enfant lors du test de neurodeveloppement)
      • po_w_kg_3cat (poids de l’enfant à la naissance
      • po_he_3cat (taille de l’enfant à la naissance
      • mo_dipl_2cat (niveau de diplome de la mère)
      • mo_age (âge maternel)
      • mo_bmi_bepr_3cat (IMC maternel avant la grossesse)
      • ch_sex (sexe de l’enfant)
      • mo_par_2cat (parité)
      • ch_bf_duration_till48w_4cat (durée de la l’allaitement)
      • po_gd (durée de la gestation)
      • po_delmod (mode d’accouchement
      • ch_food_intro_Y1_3cat (période d’introduction de la nourriture solide)
      • mo_pets (présence d’animaux)
      • ch_antibio_Y1_2cat (prise d’antibiotique entre la naissance et l’âge de 1 an)
      • home_total_y3 (score HOME à 3 ans)
      • mo_hadtotscore_grt3_imp (score d’anxiété et de dépression de la mère lors du 3ème trimestre de la grossesse)
      • mo_tob_gr_anyt_yn_n2 (tabagisme actif de la mère pendant la grossesse)
      • ch_tabacco_passive_up_to_Y1 (tabagisme périnatal passif de l’enfant (tabagisme passif de la mère pendant la grossesse + tabagisme passif de l’enfant de la naissance à l’âge de 1 an)
      • ch_care_main_6m_12m_opt2_2c (mode de garde principal de l’enfant jusqu’à l’âge de 1 an)
    • La différence avec le premier modèle multivarié porte sur la variable mode de garde

Tous les outcomes sont en continue, sans transformation.

Les variables de microbiote ne sont pas encore inclues dans ces modèles.

CBCL 2Y

Interne score Y2

Table 7:

Influence of maternal and child characteristics on the CBCL interne score at 2 years.

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3361 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 336 0.5 -0.6, 1.6 0.367





Birth weight









    <3 Kg 70 (21%)


    3-3.4 Kg 166 (49%) 0.8 -0.6, 2.1 0.265 1.0 -0.6, 2.6 0.215 0.9 -0.6, 2.5 0.240
    ≥3.5 Kg 100 (30%) 0.9 -0.6, 2.3 0.246 1.5 -0.5, 3.5 0.149 1.4 -0.6, 3.4 0.161
Birth length (cm) 335 0.0 -0.2, 0.3 0.749





Birth length









    <50 cm 123 (37%)


    50-51 cm 135 (40%) 0.2 -1.0, 1.3 0.783 -0.3 -1.7, 1.1 0.701 -0.3 -1.7, 1.1 0.706
    ≥52 cm 77 (23%) 0.0 -1.4, 1.4 0.995 -0.6 -2.4, 1.3 0.560 -0.5 -2.4, 1.3 0.576
Weight at one year (Kg) 331 -0.1 -0.6, 0.4 0.648





Weight at one year









    <8.5 Kg 61 (18%)






    8.5-9.9 Kg 181 (55%) -0.4 -1.8, 1.0 0.593





    ≥10 Kg 89 (27%) -0.4 -2.0, 1.2 0.630





Length at one year (cm) 324 -0.1 -0.3, 0.1 0.263





Length at one year









    <75 cm 121 (37%)






    75-77.9 cm 118 (36%) -1.5 -2.7, -0.3 0.012





    ≥78 cm 85 (26%) -0.7 -2.0, 0.5 0.259





Weight at 3 years (Kg) 307 -0.2 -0.6, 0.1 0.142





Weight at 3 years









    9-13 Kg 104 (34%)






    14 Kg 103 (34%) -1.3 -2.6, 0.0 0.052





    15-20 Kg 100 (33%) -0.8 -2.1, 0.5 0.227





Length at 3 years (cm) 306 -0.1 -0.3, 0.0 0.125





Length at 3 years









    81-93 cm 94 (31%)






    94-95 cm 109 (36%) -0.2 -1.5, 1.2 0.802





    96-106 cm 103 (34%) -0.7 -2.0, 0.7 0.327





Child sex









    Male 181 (54%)


    Female 155 (46%) 0.2 -0.9, 1.2 0.739 0.6 -0.5, 1.7 0.295 0.6 -0.5, 1.7 0.308
Maternal education









    ≥5 years after graduation 191 (57%)






    3-4 years after graduation 91 (27%) 0.0 -1.2, 1.2 0.977





    2 years or less after graduation 52 (16%) 0.4 -1.1, 1.9 0.611





Maternal education









    ≥5 years after graduation 191 (57%)


    <5 years after graduation 143 (43%) 0.1 -0.9, 1.2 0.777 -0.2 -1.2, 0.9 0.762 -0.2 -1.2, 0.9 0.747
Maternal age at conception (years) 336 -0.1 -0.3, 0.0 0.049 -0.1 -0.3, 0.0 0.147 -0.1 -0.3, 0.0 0.142
Maternal BMI before pregnancy (kg/m2) 335 0.0 -0.1, 0.2 0.563





Maternal BMI before pregnancy









    <19 Kg/m2 47 (14%)


    19-23.9 Kg/m2 209 (62%) 0.1 -1.4, 1.7 0.856 0.4 -1.1, 1.9 0.622 0.4 -1.1, 1.9 0.600
    ≥24 Kg/m2 79 (24%) 0.6 -1.1, 2.3 0.489 0.5 -1.2, 2.3 0.572 0.5 -1.3, 2.2 0.581
Maternal parity









    None 157 (47%)


    1 child or more 179 (53%) -1.2 -2.2, -0.2 0.022 -1.5 -2.7, -0.4 0.009 -1.6 -2.7, -0.4 0.008
Breastfeeding duration









    Not breastfed 28 (8.5%)


    <24 weeks 114 (35%) -0.2 -2.2, 1.8 0.833 -0.1 -2.1, 1.9 0.952 0.0 -2.0, 2.0 0.962
    24-47 weeks 113 (34%) -0.3 -2.3, 1.7 0.803 0.1 -1.9, 2.2 0.887 0.2 -1.9, 2.2 0.876
    Still breastfeed at 48 weeks 73 (22%) 0.8 -1.3, 2.9 0.434 0.9 -1.1, 3.0 0.375 0.9 -1.2, 3.0 0.392
Gestational duration, completed weeks 336 0.2 -0.1, 0.5 0.229 0.1 -0.3, 0.5 0.648 0.1 -0.3, 0.5 0.619
Delivery mode









    Vaginal delivery 282 (84%)


    C-section 54 (16%) -0.2 -1.6, 1.2 0.805 -0.4 -1.9, 1.1 0.595 -0.4 -1.8, 1.1 0.631
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 247 (80%)


    Between 6 and 12 months old 47 (15%) -0.1 -1.6, 1.5 0.946 -0.7 -2.3, 0.9 0.365 -0.8 -2.4, 0.9 0.352
    Not introduced at 12 months old 13 (4.2%) -0.7 -3.4, 2.0 0.588 0.5 -2.4, 3.3 0.746 0.4 -2.4, 3.2 0.761
Presence of pets









    No 214 (72%)


    One or more 83 (28%) 0.3 -0.9, 1.5 0.589 0.3 -1.0, 1.6 0.648 0.3 -1.0, 1.6 0.666
Antibiotics use between 0-12 months old









    No 230 (69%)


    Yes 105 (31%) -0.7 -1.8, 0.4 0.220 -0.6 -1.8, 0.5 0.279 -0.6 -1.8, 0.5 0.277
Learning materials score at 3 years of age (HOME questionnaire) 302 -0.3 -0.7, 0.1 0.124





Language stimulation score at 3 years of age (HOME questionnaire) 302 -0.6 -1.3, 0.1 0.094





Academic stimulation score at 3 years of age (HOME questionnaire) 302 0.0 -0.6, 0.6 0.938





Variety score at 3 years of age (HOME questionnaire) 302 -0.4 -0.9, 0.1 0.091





HOME questionnaire total score 302 -0.2 -0.4, 0.0 0.050 -0.2 -0.4, 0.0 0.096 -0.2 -0.4, 0.0 0.093
Maternal anxiety score during the third trimester of pregnancy 329 0.3 0.1, 0.5 0.001





Maternal depression score during the third trimester of pregnancy 327 0.3 0.1, 0.4 0.008





Maternal anxiety and depression score during the third trimester of pregnancy 327 0.2 0.1, 0.3 <0.001 0.2 0.1, 0.4 <0.001 0.2 0.1, 0.4 <0.001
Maternal anxiety score when child is one year old 268 0.4 0.3, 0.6 <0.001





Maternal depression score when child is one year old 268 0.5 0.3, 0.7 <0.001





Maternal anxiety and depression score when child is one year old 268 0.3 0.2, 0.5 <0.001





Maternal active smoking during pregnancy









    No 294 (94%)


    Yes 18 (5.8%) -0.1 -2.3, 2.1 0.926 -0.2 -2.8, 2.4 0.888 -0.2 -2.8, 2.4 0.892
Maternal passive smoking during pregnancy









    No 262 (81%)






    Yes 61 (19%) 1.3 0.0, 2.7 0.051





Child passive smoking during the first year of life









    No 259 (77%)






    Yes 77 (23%) 1.1 -0.1, 2.3 0.081





Child perinatal exposure to tabacco up to one year









    No 210 (65%)






    Yes 112 (35%) 1.1 0.0, 2.2 0.052





Child perinatal passive smoking up to one year









    No 217 (67%)


    Yes 109 (33%) 1.2 0.1, 2.3 0.040 0.9 -0.3, 2.0 0.127 0.9 -0.3, 2.0 0.125
Maternal alcohol consumption during pregnancy









    Did not drink 105 (32%)






    Drank only before finding out she was pregnant 158 (47%) -2.1 -3.3, -1.0 <0.001





    Drank 70 (21%) -1.9 -3.3, -0.5 0.009





Maternal alcohol consumption during pregnancy









    Did not drink 105 (32%)






    Drank only before finding out she was pregnant 158 (47%) -2.1 -3.3, -1.0 <0.001





    <1drink/month when she knew she was pregnant 59 (18%) -1.9 -3.4, -0.4 0.012





    >1drink/month when she knew she was pregnant 11 (3.3%) -1.8 -4.8, 1.1 0.215





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 199 (63%)






    Other 118 (37%) -0.3 -1.4, 0.8 0.571





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 260 (82%)




    Other 57 (18%) -0.4 -1.8, 0.9 0.531 -0.5 -2.0, 0.9 0.473


Main mode of child care up to 1 year









    Collective day care 266 (84%)




    Other 51 (16%) -0.1 -1.5, 1.4 0.912


-0.1 -1.6, 1.4 0.864
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 59 (19%)






    Nursery assistant (out child home) 140 (44%) 0.2 -1.3, 1.7 0.794





    Other 118 (37%) -0.2 -1.7, 1.3 0.816





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 98 (31%)






    Nursery assistant (out child home) 162 (51%) 0.1 -1.1, 1.3 0.824





    Other 57 (18%) -0.4 -1.9, 1.2 0.658





Main mode of child care up to 1 year









    Collective day care 101 (32%)






    Nursery assistant (out child home) 165 (52%) -0.1 -1.3, 1.1 0.883





    Other 51 (16%) -0.1 -1.8, 1.5 0.868





Paternal education









    ≥5 years after graduation 152 (64%)






    3-4 years after graduation 40 (17%) 1.2 -0.5, 2.9 0.164





    2 years or less after graduation 46 (19%) -0.2 -1.8, 1.4 0.849





Paternal age at child birth (years) 301 -0.2 -0.3, -0.1 <0.001





Paternal age at child birth









    23-31 years 97 (32%)






    32-36 years 105 (35%) -1.1 -2.4, 0.2 0.092





    37-72 years 99 (33%) -2.2 -3.6, -0.9 <0.001





Child age at the CBCL 2 years evaluation 336 0.1 -0.1, 0.3 0.292





Child age at the CBCL 2 years evaluation



0.1 -0.1, 0.3 0.365 0.1 -0.1, 0.3 0.380
No. Obs.



336

336





0.125

0.123

Adjusted R²



0.054

0.052

1 N; n (%)
2 CI = Confidence Interval
Figure 64: Multivariate model hypothesis checking (outcome is CBCL interne score Y2, before inclusion of microbiota variables)

Externe score Y2

Table 8:

Influence of maternal and child characteristics on the CBCL externe score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3351 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 335 0.2 -1.3, 1.7 0.786





Birth weight









    <3 Kg 70 (21%)


    3-3.4 Kg 166 (50%) 0.0 -1.7, 1.8 0.981 -0.5 -2.7, 1.6 0.611 -0.6 -2.7, 1.5 0.571
    ≥3.5 Kg 99 (30%) 0.5 -1.5, 2.4 0.630 -0.1 -2.8, 2.6 0.940 -0.1 -2.8, 2.5 0.914
Birth length (cm) 334 0.0 -0.3, 0.3 0.913





Birth length









    <50 cm 123 (37%)


    50-51 cm 134 (40%) 0.2 -1.3, 1.7 0.801 -0.3 -2.1, 1.6 0.789 -0.2 -2.1, 1.6 0.795
    ≥52 cm 77 (23%) 0.6 -1.2, 2.4 0.545 0.1 -2.4, 2.6 0.917 0.2 -2.4, 2.7 0.900
Weight at one year (Kg) 330 0.0 -0.6, 0.7 0.888





Weight at one year









    <8.5 Kg 61 (18%)






    8.5-9.9 Kg 180 (55%) 0.7 -1.2, 2.5 0.472





    ≥10 Kg 89 (27%) 0.5 -1.6, 2.5 0.645





Length at one year (cm) 323 -0.1 -0.3, 0.2 0.598





Length at one year









    <75 cm 121 (37%)






    75-77.9 cm 117 (36%) 0.1 -1.5, 1.7 0.912





    ≥78 cm 85 (26%) 0.6 -1.1, 2.3 0.500





Weight at 3 years (Kg) 306 0.0 -0.4, 0.4 0.973





Weight at 3 years









    9-13 Kg 104 (34%)






    14 Kg 102 (33%) -0.5 -2.2, 1.3 0.581





    15-20 Kg 100 (33%) 0.2 -1.5, 2.0 0.802





Length at 3 years (cm) 305 0.0 -0.2, 0.2 0.827





Length at 3 years









    81-93 cm 94 (31%)






    94-95 cm 108 (35%) 1.6 -0.2, 3.3 0.075





    96-106 cm 103 (34%) 0.0 -1.7, 1.8 0.986





Child sex









    Male 180 (54%)


    Female 155 (46%) -0.9 -2.2, 0.5 0.217 -0.3 -1.8, 1.2 0.702 -0.3 -1.8, 1.2 0.690
Maternal education









    ≥5 years after graduation 191 (57%)






    3-4 years after graduation 90 (27%) 1.1 -0.4, 2.7 0.157





    2 years or less after graduation 52 (16%) 1.4 -0.5, 3.3 0.159





Maternal education









    ≥5 years after graduation 191 (57%)


    <5 years after graduation 142 (43%) 1.2 -0.1, 2.6 0.078 0.7 -0.7, 2.1 0.304 0.7 -0.7, 2.1 0.313
Maternal age at conception (years) 335 -0.2 -0.3, 0.0 0.065 -0.2 -0.4, 0.0 0.053 -0.2 -0.4, 0.0 0.052
Maternal BMI before pregnancy (kg/m2) 334 0.1 -0.1, 0.3 0.178





Maternal BMI before pregnancy









    <19 Kg/m2 47 (14%)


    19-23.9 Kg/m2 209 (63%) 0.9 -1.1, 2.9 0.387 0.9 -1.1, 3.0 0.383 0.9 -1.1, 3.0 0.372
    ≥24 Kg/m2 78 (23%) 0.9 -1.4, 3.2 0.432 0.7 -1.6, 3.1 0.547 0.7 -1.6, 3.1 0.554
Maternal parity









    None 157 (47%)


    1 child or more 178 (53%) -0.1 -1.4, 1.3 0.930 -0.2 -1.7, 1.3 0.811 -0.2 -1.7, 1.3 0.770
Breastfeeding duration









    Not breastfed 28 (8.6%)


    <24 weeks 113 (35%) -0.5 -3.1, 2.2 0.727 -0.1 -2.8, 2.6 0.941 -0.1 -2.8, 2.6 0.947
    24-47 weeks 113 (35%) -0.8 -3.4, 1.8 0.556 0.1 -2.6, 2.8 0.942 0.1 -2.6, 2.8 0.935
    Still breastfeed at 48 weeks 73 (22%) 0.0 -2.8, 2.7 0.974 0.4 -2.4, 3.2 0.777 0.4 -2.4, 3.2 0.797
Gestational duration, completed weeks 335 0.1 -0.3, 0.6 0.557 0.1 -0.4, 0.6 0.663 0.1 -0.4, 0.7 0.639
Delivery mode









    Vaginal delivery 281 (84%)


    C-section 54 (16%) 0.1 -1.8, 1.9 0.939 -0.1 -2.1, 1.9 0.934 0.0 -2.0, 1.9 0.968
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 247 (80%)


    Between 6 and 12 months old 47 (15%) -0.4 -2.4, 1.6 0.701 -0.8 -2.8, 1.3 0.469 -0.8 -2.8, 1.3 0.454
    Not introduced at 12 months old 13 (4.2%) 0.6 -2.9, 4.2 0.718 0.8 -3.0, 4.6 0.672 0.8 -3.1, 4.6 0.690
Presence of pets









    No 214 (72%)


    One or more 83 (28%) -0.9 -2.5, 0.7 0.273 -1.1 -2.7, 0.5 0.183 -1.1 -2.7, 0.5 0.180
Antibiotics use between 0-12 months old









    No 229 (69%)


    Yes 105 (31%) 0.3 -1.2, 1.8 0.694 0.4 -1.1, 1.9 0.629 0.4 -1.1, 1.9 0.634
Learning materials score at 3 years of age (HOME questionnaire) 301 -0.5 -1.1, 0.0 0.046





Language stimulation score at 3 years of age (HOME questionnaire) 301 -0.6 -1.5, 0.3 0.212





Academic stimulation score at 3 years of age (HOME questionnaire) 301 -0.5 -1.3, 0.3 0.226





Variety score at 3 years of age (HOME questionnaire) 301 -0.6 -1.3, 0.0 0.058





HOME questionnaire total score 301 -0.4 -0.6, -0.1 0.010 -0.3 -0.6, 0.0 0.044 -0.3 -0.6, 0.0 0.042
Maternal anxiety score during the third trimester of pregnancy 328 0.4 0.1, 0.6 0.003





Maternal depression score during the third trimester of pregnancy 326 0.2 0.0, 0.5 0.098





Maternal anxiety and depression score during the third trimester of pregnancy 326 0.2 0.1, 0.3 0.005 0.2 0.1, 0.4 0.004 0.2 0.1, 0.4 0.004
Maternal anxiety score when child is one year old 268 0.4 0.2, 0.7 0.002





Maternal depression score when child is one year old 268 0.4 0.1, 0.7 0.006





Maternal anxiety and depression score when child is one year old 268 0.3 0.1, 0.5 <0.001





Maternal active smoking during pregnancy









    No 294 (94%)


    Yes 18 (5.8%) 2.8 -0.3, 5.8 0.072 1.6 -1.4, 4.6 0.282 1.6 -1.3, 4.6 0.280
Maternal passive smoking during pregnancy









    No 262 (81%)






    Yes 61 (19%) 1.7 -0.1, 3.4 0.059





Child passive smoking during the first year of life









    No 258 (77%)






    Yes 77 (23%) 1.2 -0.4, 2.9 0.126





Child perinatal exposure to tabacco up to one year









    No 210 (65%)






    Yes 112 (35%) 1.6 0.1, 3.0 0.034





Child perinatal passive smoking up to one year









    No 217 (67%)


    Yes 109 (33%) 1.6 0.2, 3.1 0.026 1.0 -0.5, 2.5 0.187 1.0 -0.5, 2.5 0.184
Maternal alcohol consumption during pregnancy









    Did not drink 104 (31%)






    Drank only before finding out she was pregnant 158 (48%) -1.0 -2.5, 0.6 0.231





    Drank 70 (21%) 0.1 -1.9, 2.0 0.953





Maternal alcohol consumption during pregnancy









    Did not drink 104 (31%)






    Drank only before finding out she was pregnant 158 (48%) -1.0 -2.5, 0.6 0.231





    <1drink/month when she knew she was pregnant 59 (18%) -0.2 -2.2, 1.8 0.871





    >1drink/month when she knew she was pregnant 11 (3.3%) 1.3 -2.7, 5.2 0.529





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 199 (63%)






    Other 118 (37%) -0.7 -2.2, 0.7 0.312





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 260 (82%)




    Other 57 (18%) -0.6 -2.4, 1.2 0.525 -0.6 -2.5, 1.3 0.555


Main mode of child care up to 1 year









    Collective day care 266 (84%)




    Other 51 (16%) -0.4 -2.3, 1.5 0.694


-0.2 -2.2, 1.8 0.860
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 59 (19%)






    Nursery assistant (out child home) 140 (44%) 0.4 -1.5, 2.3 0.683





    Other 118 (37%) -0.5 -2.4, 1.5 0.647





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 98 (31%)






    Nursery assistant (out child home) 162 (51%) 0.1 -1.5, 1.7 0.912





    Other 57 (18%) -0.5 -2.6, 1.5 0.614





Main mode of child care up to 1 year









    Collective day care 101 (32%)






    Nursery assistant (out child home) 165 (52%) -0.2 -1.8, 1.4 0.799





    Other 51 (16%) -0.5 -2.6, 1.6 0.642





Paternal education









    ≥5 years after graduation 152 (64%)






    3-4 years after graduation 40 (17%) 1.3 -0.9, 3.5 0.244





    2 years or less after graduation 46 (19%) 0.2 -1.9, 2.3 0.831





Paternal age at child birth (years) 301 -0.2 -0.3, 0.0 0.008





Paternal age at child birth









    23-31 years 97 (32%)






    32-36 years 105 (35%) 1.1 -0.6, 2.7 0.221





    37-72 years 99 (33%) -1.9 -3.6, -0.2 0.032





Child age at the CBCL 2 years evaluation 335 0.0 -0.3, 0.2 0.795





Child age at the CBCL 2 years evaluation



0.0 -0.3, 0.2 0.878 0.0 -0.3, 0.2 0.863
No. Obs.



335

335





0.092

0.091

Adjusted R²



0.018

0.017

1 N; n (%)
2 CI = Confidence Interval
Figure 65: Multivariate model hypothesis checking (outcome is CBCL externe score Y2, before inclusion of microbiota variables)

SRS total score 3Y

Table 9:

Influence of maternal and child characteristics on the SRS total score at 3 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3321 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 332 2.1 -0.9, 5.1 0.174





Birth weight









    <3 Kg 69 (21%)


    3-3.4 Kg 163 (49%) 1.2 -2.5, 4.8 0.523 1.6 -2.6, 5.7 0.462 1.5 -2.6, 5.7 0.474
    ≥3.5 Kg 100 (30%) 2.3 -1.7, 6.3 0.254 3.0 -2.3, 8.3 0.271 2.9 -2.4, 8.2 0.279
Birth length (cm) 331 0.2 -0.5, 0.8 0.629





Birth length









    <50 cm 121 (37%)


    50-51 cm 132 (40%) -0.3 -3.5, 2.9 0.854 -1.1 -4.8, 2.5 0.534 -1.1 -4.7, 2.5 0.538
    ≥52 cm 78 (24%) 1.1 -2.6, 4.8 0.557 -1.1 -6.0, 3.8 0.650 -1.1 -6.0, 3.8 0.664
Weight at one year (Kg) 328 0.3 -1.1, 1.6 0.692





Weight at one year









    <8.5 Kg 57 (17%)






    8.5-9.9 Kg 181 (55%) 0.6 -3.2, 4.4 0.759





    ≥10 Kg 90 (27%) 2.8 -1.5, 7.1 0.195





Length at one year (cm) 321 0.3 -0.2, 0.8 0.189





Length at one year









    <75 cm 118 (37%)






    75-77.9 cm 111 (35%) -0.9 -4.2, 2.4 0.575





    ≥78 cm 92 (29%) 3.9 0.4, 7.3 0.029





Weight at 3 years (Kg) 307 0.4 -0.5, 1.3 0.367





Weight at 3 years









    9-13 Kg 103 (34%)






    14 Kg 104 (34%) -1.8 -5.2, 1.7 0.316





    15-20 Kg 100 (33%) 1.1 -2.4, 4.6 0.522





Length at 3 years (cm) 305 0.1 -0.3, 0.5 0.490





Length at 3 years









    81-93 cm 94 (31%)






    94-95 cm 106 (35%) 0.3 -3.2, 3.8 0.861





    96-106 cm 105 (34%) 2.3 -1.3, 5.8 0.205





Child sex









    Male 177 (53%)


    Female 155 (47%) -0.3 -3.1, 2.5 0.817 0.4 -2.4, 3.3 0.762 0.5 -2.4, 3.4 0.746
Maternal education









    ≥5 years after graduation 191 (58%)






    3-4 years after graduation 90 (27%) 3.9 0.7, 7.1 0.018





    2 years or less after graduation 49 (15%) 3.2 -0.8, 7.2 0.120





Maternal education









    ≥5 years after graduation 191 (58%)


    <5 years after graduation 139 (42%) 3.7 0.8, 6.5 0.011 4.0 1.2, 6.8 0.005 4.0 1.2, 6.8 0.005
Maternal age at conception (years) 332 -0.3 -0.7, 0.1 0.105 -0.1 -0.5, 0.3 0.708 -0.1 -0.5, 0.3 0.721
Maternal BMI before pregnancy (kg/m2) 331 0.0 -0.4, 0.4 0.909





Maternal BMI before pregnancy









    <19 Kg/m2 46 (14%)


    19-23.9 Kg/m2 208 (63%) 1.2 -2.9, 5.4 0.561 2.0 -2.0, 6.0 0.325 2.0 -2.0, 6.0 0.329
    ≥24 Kg/m2 77 (23%) 1.3 -3.5, 6.0 0.599 1.7 -3.0, 6.3 0.474 1.7 -3.0, 6.3 0.482
Maternal parity









    None 151 (45%)


    1 child or more 181 (55%) -4.7 -7.5, -2.0 <0.001 -6.5 -9.5, -3.6 <0.001 -6.5 -9.5, -3.6 <0.001
Breastfeeding duration









    Not breastfed 25 (7.7%)


    <24 weeks 113 (35%) -3.2 -8.9, 2.4 0.263 -2.0 -7.4, 3.5 0.474 -2.0 -7.5, 3.4 0.466
    24-47 weeks 112 (35%) -3.9 -9.5, 1.8 0.182 -1.5 -7.0, 3.9 0.582 -1.6 -7.0, 3.9 0.577
    Still breastfeed at 48 weeks 74 (23%) -4.4 -10.4, 1.5 0.143 -2.8 -8.5, 2.9 0.335 -2.8 -8.6, 2.9 0.328
Gestational duration, completed weeks 332 0.6 -0.3, 1.5 0.188 0.4 -0.6, 1.4 0.388 0.4 -0.6, 1.4 0.383
Delivery mode









    Vaginal delivery 278 (84%)


    C-section 54 (16%) 1.1 -2.7, 4.8 0.583 -0.4 -4.2, 3.5 0.842 -0.4 -4.2, 3.5 0.848
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 238 (79%)


    Between 6 and 12 months old 49 (16%) 0.6 -3.4, 4.5 0.784 -1.7 -5.8, 2.4 0.403 -1.7 -5.8, 2.3 0.401
    Not introduced at 12 months old 15 (5.0%) 6.0 -0.8, 12.7 0.083 6.6 -0.3, 13.5 0.059 6.7 -0.2, 13.6 0.056
Presence of pets









    No 211 (72%)


    One or more 83 (28%) 0.1 -3.2, 3.4 0.944 -0.3 -3.9, 3.3 0.865 -0.3 -3.9, 3.3 0.865
Antibiotics use between 0-12 months old









    No 228 (69%)


    Yes 103 (31%) -0.2 -3.2, 2.8 0.894 0.0 -3.0, 3.0 0.989 0.0 -3.0, 3.0 0.981
Learning materials score at 3 years of age (HOME questionnaire) 303 -1.3 -2.3, -0.2 0.019





Language stimulation score at 3 years of age (HOME questionnaire) 303 -1.8 -3.5, 0.0 0.052





Academic stimulation score at 3 years of age (HOME questionnaire) 303 -0.8 -2.5, 0.8 0.323





Variety score at 3 years of age (HOME questionnaire) 303 -1.2 -2.6, 0.1 0.062





HOME questionnaire total score 303 -0.8 -1.3, -0.3 0.004 -0.7 -1.2, -0.1 0.018 -0.7 -1.2, -0.1 0.018
Maternal anxiety score during the third trimester of pregnancy 323 0.6 0.1, 1.1 0.012





Maternal depression score during the third trimester of pregnancy 322 0.8 0.3, 1.3 0.002





Maternal anxiety and depression score during the third trimester of pregnancy 321 0.5 0.2, 0.8 <0.001 0.6 0.3, 1.0 <0.001 0.6 0.3, 0.9 <0.001
Maternal anxiety score when child is one year old 260 0.9 0.4, 1.4 <0.001





Maternal depression score when child is one year old 260 1.0 0.4, 1.5 <0.001





Maternal anxiety and depression score when child is one year old 260 0.7 0.4, 1.0 <0.001





Maternal active smoking during pregnancy









    No 290 (94%)


    Yes 19 (6.1%) -1.0 -6.9, 4.9 0.737 -0.7 -7.0, 5.6 0.832 -0.7 -6.9, 5.6 0.833
Maternal passive smoking during pregnancy









    No 261 (82%)






    Yes 57 (18%) -0.1 -3.8, 3.6 0.965





Child passive smoking during the first year of life









    No 257 (77%)






    Yes 75 (23%) -0.2 -3.5, 3.1 0.900





Child perinatal exposure to tabacco up to one year









    No 211 (67%)






    Yes 106 (33%) -0.6 -3.6, 2.4 0.689





Child perinatal passive smoking up to one year









    No 218 (68%)


    Yes 103 (32%) -0.7 -3.7, 2.3 0.653 -1.7 -5.0, 1.5 0.300 -1.7 -5.0, 1.6 0.306
Maternal alcohol consumption during pregnancy









    Did not drink 99 (30%)






    Drank only before finding out she was pregnant 159 (48%) -1.1 -4.3, 2.2 0.524





    Drank 72 (22%) -1.8 -5.7, 2.1 0.369





Maternal alcohol consumption during pregnancy









    Did not drink 99 (30%)






    Drank only before finding out she was pregnant 159 (48%) -1.1 -4.3, 2.2 0.524





    <1drink/month when she knew she was pregnant 61 (18%) -2.1 -6.3, 2.0 0.310





    >1drink/month when she knew she was pregnant 11 (3.3%) 0.1 -8.0, 8.2 0.982





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 198 (63%)






    Other 117 (37%) 0.5 -2.4, 3.5 0.736





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 257 (82%)




    Other 58 (18%) -1.4 -5.1, 2.3 0.456 -0.9 -4.8, 2.9 0.625


Main mode of child care up to 1 year









    Collective day care 264 (84%)




    Other 51 (16%) -1.6 -5.5, 2.2 0.407


-0.9 -4.8, 3.0 0.647
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 57 (18%)






    Nursery assistant (out child home) 141 (45%) 4.4 0.4, 8.3 0.031





    Other 117 (37%) 3.6 -0.5, 7.7 0.082





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 96 (30%)






    Nursery assistant (out child home) 161 (51%) 1.6 -1.7, 4.8 0.345





    Other 58 (18%) -0.4 -4.6, 3.8 0.847





Main mode of child care up to 1 year









    Collective day care 99 (31%)






    Nursery assistant (out child home) 165 (52%) 1.9 -1.3, 5.1 0.237





    Other 51 (16%) -0.4 -4.8, 3.9 0.849





Paternal education









    ≥5 years after graduation 151 (64%)






    3-4 years after graduation 41 (17%) 3.2 -1.4, 7.7 0.169





    2 years or less after graduation 43 (18%) 1.4 -3.0, 5.8 0.539





Paternal age at child birth (years) 299 -0.3 -0.6, 0.0 0.052





Paternal age at child birth









    23-31 years 97 (32%)






    32-36 years 103 (34%) -4.5 -8.1, -1.0 0.013





    37-72 years 99 (33%) -5.0 -8.6, -1.4 0.007





Child age at the SRS 3 years evaluation 332 0.3 0.0, 0.6 0.081





Child age at the SRS 3 years evaluation



0.2 -0.1, 0.5 0.280 0.2 -0.1, 0.5 0.284
No. Obs.



332

332





0.171

0.171

Adjusted R²



0.104

0.103

1 N; n (%)
2 CI = Confidence Interval
Figure 66: Multivariate model hypothesis checking (outcome is SRS total score Y3, before inclusion of microbiota variables)

BRIEF-P Y3

Inhibit score Y3

Table 10:

Influence of maternal and child characteristics on the BRIEF-P inhibit score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3301 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 330 0.2 -1.0, 1.4 0.704





Birth weight









    <3 Kg 68 (21%)


    3-3.4 Kg 161 (49%) 0.1 -1.4, 1.5 0.931 -0.5 -2.2, 1.3 0.607 -0.5 -2.3, 1.2 0.559
    ≥3.5 Kg 101 (31%) 0.0 -1.6, 1.6 0.993 -1.2 -3.4, 1.0 0.297 -1.2 -3.5, 1.0 0.272
Birth length (cm) 329 0.1 -0.2, 0.3 0.508





Birth length









    <50 cm 118 (36%)


    50-51 cm 131 (40%) 0.8 -0.5, 2.1 0.230 1.1 -0.5, 2.6 0.171 1.1 -0.5, 2.6 0.175
    ≥52 cm 80 (24%) 1.3 -0.1, 2.8 0.074 2.0 0.0, 4.0 0.055 2.0 0.0, 4.0 0.050
Weight at one year (Kg) 326 0.3 -0.3, 0.8 0.330





Weight at one year









    <8.5 Kg 55 (17%)






    8.5-9.9 Kg 179 (55%) 1.3 -0.3, 2.8 0.114





    ≥10 Kg 92 (28%) 2.0 0.3, 3.7 0.021





Length at one year (cm) 319 0.2 0.0, 0.4 0.065





Length at one year









    <75 cm 116 (36%)






    75-77.9 cm 112 (35%) 0.6 -0.7, 2.0 0.340





    ≥78 cm 91 (29%) 2.0 0.6, 3.4 0.005





Weight at 3 years (Kg) 305 0.4 0.0, 0.7 0.034





Weight at 3 years









    9-13 Kg 102 (33%)






    14 Kg 103 (34%) 0.1 -1.3, 1.5 0.882





    15-20 Kg 100 (33%) 1.3 -0.1, 2.7 0.073





Length at 3 years (cm) 303 0.2 0.0, 0.4 0.010





Length at 3 years









    81-93 cm 93 (31%)






    94-95 cm 104 (34%) 1.3 -0.1, 2.7 0.070





    96-106 cm 106 (35%) 1.9 0.5, 3.3 0.009





Child sex









    Male 175 (53%)


    Female 155 (47%) -1.2 -2.3, 0.0 0.042 -0.7 -1.9, 0.5 0.237 -0.7 -2.0, 0.5 0.228
Maternal education









    ≥5 years after graduation 190 (58%)






    3-4 years after graduation 89 (27%) 0.7 -0.6, 2.0 0.276





    2 years or less after graduation 49 (15%) 1.0 -0.6, 2.6 0.217





Maternal education









    ≥5 years after graduation 190 (58%)


    <5 years after graduation 138 (42%) 0.8 -0.3, 1.9 0.151 0.8 -0.4, 2.0 0.189 0.8 -0.4, 1.9 0.201
Maternal age at conception (years) 330 -0.1 -0.2, 0.0 0.191 -0.1 -0.2, 0.1 0.488 -0.1 -0.2, 0.1 0.473
Maternal BMI before pregnancy (kg/m2) 329 0.0 -0.1, 0.2 0.725





Maternal BMI before pregnancy









    <19 Kg/m2 46 (14%)


    19-23.9 Kg/m2 208 (63%) 0.9 -0.8, 2.5 0.309 0.8 -0.8, 2.5 0.321 0.9 -0.8, 2.6 0.303
    ≥24 Kg/m2 75 (23%) 0.7 -1.2, 2.6 0.493 0.6 -1.3, 2.6 0.536 0.6 -1.3, 2.5 0.545
Maternal parity









    None 148 (45%)


    1 child or more 182 (55%) -1.0 -2.1, 0.1 0.083 -1.5 -2.7, -0.2 0.021 -1.5 -2.8, -0.3 0.018
Breastfeeding duration









    Not breastfed 24 (7.5%)


    <24 weeks 114 (35%) -0.3 -2.5, 2.0 0.813 0.1 -2.2, 2.4 0.936 0.1 -2.2, 2.5 0.907
    24-47 weeks 109 (34%) -0.3 -2.5, 2.0 0.829 0.6 -1.8, 3.0 0.627 0.6 -1.8, 3.0 0.602
    Still breastfeed at 48 weeks 75 (23%) 0.4 -2.0, 2.7 0.760 1.1 -1.3, 3.5 0.382 1.1 -1.4, 3.5 0.391
Gestational duration, completed weeks 330 0.0 -0.4, 0.3 0.790 -0.1 -0.5, 0.3 0.690 -0.1 -0.5, 0.4 0.738
Delivery mode









    Vaginal delivery 276 (84%)


    C-section 54 (16%) 0.5 -1.0, 2.0 0.505 0.0 -1.6, 1.7 0.958 0.1 -1.5, 1.7 0.901
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 236 (79%)


    Between 6 and 12 months old 48 (16%) 0.1 -1.5, 1.7 0.933 -0.6 -2.3, 1.0 0.461 -0.6 -2.3, 1.0 0.445
    Not introduced at 12 months old 15 (5.0%) 2.2 -0.4, 4.9 0.102 1.8 -1.0, 4.6 0.205 1.7 -1.0, 4.5 0.218
Presence of pets









    No 209 (72%)


    One or more 83 (28%) 0.3 -1.0, 1.6 0.625 0.1 -1.3, 1.6 0.878 0.1 -1.4, 1.5 0.915
Antibiotics use between 0-12 months old









    No 229 (70%)


    Yes 100 (30%) -0.2 -1.4, 1.0 0.793 0.0 -1.2, 1.3 0.958 0.0 -1.2, 1.3 0.965
Learning materials score at 3 years of age (HOME questionnaire) 301 0.0 -0.5, 0.4 0.880





Language stimulation score at 3 years of age (HOME questionnaire) 301 -0.2 -0.9, 0.5 0.614





Academic stimulation score at 3 years of age (HOME questionnaire) 301 0.1 -0.6, 0.7 0.861





Variety score at 3 years of age (HOME questionnaire) 301 -0.4 -0.9, 0.1 0.144





HOME questionnaire total score 301 -0.1 -0.3, 0.1 0.442 -0.1 -0.3, 0.2 0.538 -0.1 -0.3, 0.2 0.522
Maternal anxiety score during the third trimester of pregnancy 321 0.2 0.0, 0.4 0.069





Maternal depression score during the third trimester of pregnancy 321 0.2 0.0, 0.4 0.023





Maternal anxiety and depression score during the third trimester of pregnancy 320 0.1 0.0, 0.3 0.014 0.2 0.0, 0.3 0.017 0.2 0.0, 0.3 0.019
Maternal anxiety score when child is one year old 258 0.1 -0.1, 0.3 0.230





Maternal depression score when child is one year old 258 0.3 0.1, 0.5 0.008





Maternal anxiety and depression score when child is one year old 258 0.2 0.0, 0.3 0.022





Maternal active smoking during pregnancy









    No 288 (94%)


    Yes 19 (6.2%) 0.5 -1.9, 2.9 0.680 -0.1 -2.7, 2.5 0.943 -0.1 -2.7, 2.5 0.957
Maternal passive smoking during pregnancy









    No 259 (82%)






    Yes 57 (18%) -0.1 -1.6, 1.4 0.914





Child passive smoking during the first year of life









    No 256 (78%)






    Yes 74 (22%) 0.2 -1.1, 1.6 0.715





Child perinatal exposure to tabacco up to one year









    No 209 (66%)






    Yes 106 (34%) 0.5 -0.7, 1.7 0.429





Child perinatal passive smoking up to one year









    No 216 (68%)


    Yes 103 (32%) 0.5 -0.7, 1.7 0.411 0.3 -1.1, 1.7 0.667 0.3 -1.1, 1.7 0.653
Maternal alcohol consumption during pregnancy









    Did not drink 99 (30%)






    Drank only before finding out she was pregnant 157 (48%) -0.3 -1.6, 1.0 0.639





    Drank 72 (22%) -0.9 -2.5, 0.7 0.251





Maternal alcohol consumption during pregnancy









    Did not drink 99 (30%)






    Drank only before finding out she was pregnant 157 (48%) -0.3 -1.6, 1.0 0.639





    <1drink/month when she knew she was pregnant 61 (19%) -1.0 -2.6, 0.7 0.242





    >1drink/month when she knew she was pregnant 11 (3.4%) -0.6 -3.8, 2.7 0.735





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 194 (62%)






    Other 118 (38%) -0.1 -1.3, 1.1 0.830





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 255 (82%)




    Other 57 (18%) -0.6 -2.1, 0.9 0.449 -0.5 -2.1, 1.0 0.497


Main mode of child care up to 1 year









    Collective day care 262 (84%)




    Other 50 (16%) -0.2 -1.7, 1.4 0.823


0.0 -1.7, 1.7 >0.999
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 56 (18%)






    Nursery assistant (out child home) 138 (44%) 1.2 -0.4, 2.8 0.144





    Other 118 (38%) 0.7 -0.9, 2.4 0.389





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 95 (30%)






    Nursery assistant (out child home) 160 (51%) 0.8 -0.6, 2.1 0.258





    Other 57 (18%) -0.1 -1.8, 1.6 0.910





Main mode of child care up to 1 year









    Collective day care 98 (31%)






    Nursery assistant (out child home) 164 (53%) 0.7 -0.6, 2.0 0.320





    Other 50 (16%) 0.2 -1.5, 2.0 0.796





Paternal education









    ≥5 years after graduation 149 (64%)






    3-4 years after graduation 41 (18%) -0.2 -2.0, 1.6 0.829





    2 years or less after graduation 44 (19%) 0.8 -0.9, 2.5 0.355





Paternal age at child birth (years) 296 -0.1 -0.2, 0.1 0.295





Paternal age at child birth









    23-31 years 97 (33%)






    32-36 years 98 (33%) -1.4 -2.8, 0.1 0.063





    37-72 years 101 (34%) -1.5 -3.0, -0.1 0.034





Child age at the SRS 3 years evaluation 330 0.1 0.0, 0.2 0.076





Child age at the SRS 3 years evaluation



0.1 0.0, 0.2 0.119 0.1 0.0, 0.2 0.122
No. Obs.



330

330





0.097

0.095

Adjusted R²



0.022

0.021

1 N; n (%)
2 CI = Confidence Interval
Figure 67: Multivariate model hypothesis checking (outcome is BRIEF-P inhibit score Y3, before inclusion of microbiota variables)

Shift score Y3

Table 11:

Influence of maternal and child characteristics on the BRIEF-P shift score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3381 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 338 0.5 -0.2, 1.2 0.178





Birth weight









    <3 Kg 70 (21%)


    3-3.4 Kg 166 (49%) 0.2 -0.7, 1.0 0.703 -0.2 -1.2, 0.8 0.736 -0.1 -1.1, 0.9 0.839
    ≥3.5 Kg 102 (30%) 0.6 -0.3, 1.5 0.218 0.3 -1.0, 1.6 0.629 0.4 -0.9, 1.6 0.548
Birth length (cm) 337 0.1 -0.1, 0.2 0.399





Birth length









    <50 cm 121 (36%)


    50-51 cm 135 (40%) 0.4 -0.4, 1.1 0.312 0.2 -0.6, 1.1 0.583 0.2 -0.6, 1.1 0.602
    ≥52 cm 81 (24%) 0.3 -0.5, 1.2 0.420 0.3 -0.9, 1.4 0.656 0.2 -1.0, 1.4 0.735
Weight at one year (Kg) 334 0.1 -0.2, 0.4 0.713





Weight at one year









    <8.5 Kg 58 (17%)






    8.5-9.9 Kg 182 (54%) -0.3 -1.1, 0.6 0.559





    ≥10 Kg 94 (28%) 0.4 -0.5, 1.4 0.362





Length at one year (cm) 327 0.1 0.0, 0.2 0.223





Length at one year









    <75 cm 119 (36%)






    75-77.9 cm 116 (35%) 0.1 -0.6, 0.8 0.781





    ≥78 cm 92 (28%) 0.6 -0.2, 1.4 0.119





Weight at 3 years (Kg) 313 -0.1 -0.3, 0.1 0.566





Weight at 3 years









    9-13 Kg 105 (34%)






    14 Kg 104 (33%) -0.4 -1.2, 0.4 0.322





    15-20 Kg 104 (33%) -0.2 -1.0, 0.6 0.641





Length at 3 years (cm) 311 0.0 -0.1, 0.1 0.494





Length at 3 years









    81-93 cm 95 (31%)






    94-95 cm 109 (35%) 0.2 -0.6, 1.0 0.599





    96-106 cm 107 (34%) 0.3 -0.5, 1.1 0.420





Child sex









    Male 181 (54%)


    Female 157 (46%) 0.1 -0.5, 0.7 0.721 0.3 -0.4, 0.9 0.467 0.2 -0.5, 0.9 0.512
Maternal education









    ≥5 years after graduation 195 (58%)






    3-4 years after graduation 90 (27%) 0.2 -0.6, 0.9 0.623





    2 years or less after graduation 51 (15%) 0.4 -0.5, 1.3 0.379





Maternal education









    ≥5 years after graduation 195 (58%)


    <5 years after graduation 141 (42%) 0.3 -0.4, 0.9 0.415 0.4 -0.3, 1.1 0.223 0.4 -0.3, 1.1 0.246
Maternal age at conception (years) 338 0.0 -0.1, 0.0 0.381 0.0 -0.1, 0.0 0.297 0.0 -0.1, 0.0 0.283
Maternal BMI before pregnancy (kg/m2) 337 0.0 -0.1, 0.0 0.302





Maternal BMI before pregnancy









    <19 Kg/m2 46 (14%)


    19-23.9 Kg/m2 213 (63%) -0.5 -1.5, 0.4 0.257 -0.3 -1.3, 0.6 0.492 -0.3 -1.3, 0.6 0.496
    ≥24 Kg/m2 78 (23%) -0.6 -1.7, 0.4 0.240 -0.6 -1.7, 0.5 0.251 -0.6 -1.7, 0.5 0.275
Maternal parity









    None 154 (46%)


    1 child or more 184 (54%) -0.5 -1.2, 0.1 0.099 -0.8 -1.5, -0.1 0.023 -0.8 -1.5, -0.1 0.026
Breastfeeding duration









    Not breastfed 26 (7.9%)


    <24 weeks 115 (35%) 0.4 -0.9, 1.7 0.546 0.7 -0.5, 2.0 0.266 0.7 -0.5, 2.0 0.251
    24-47 weeks 112 (34%) 1.1 -0.2, 2.3 0.099 1.5 0.2, 2.8 0.021 1.5 0.2, 2.8 0.021
    Still breastfeed at 48 weeks 77 (23%) 0.9 -0.4, 2.2 0.185 1.1 -0.2, 2.5 0.094 1.2 -0.2, 2.5 0.086
Gestational duration, completed weeks 338 0.1 -0.1, 0.3 0.357 0.1 -0.2, 0.3 0.562 0.1 -0.2, 0.3 0.610
Delivery mode









    Vaginal delivery 282 (83%)


    C-section 56 (17%) 0.2 -0.6, 1.1 0.577 0.2 -0.7, 1.1 0.608 0.2 -0.7, 1.1 0.659
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 243 (79%)


    Between 6 and 12 months old 49 (16%) 0.0 -0.9, 0.9 0.975 -0.6 -1.5, 0.3 0.205 -0.6 -1.5, 0.3 0.218
    Not introduced at 12 months old 15 (4.9%) -0.1 -1.6, 1.4 0.902 0.0 -1.7, 1.7 0.998 0.0 -1.8, 1.7 0.961
Presence of pets









    No 215 (72%)


    One or more 84 (28%) -0.2 -1.0, 0.5 0.562 -0.4 -1.3, 0.4 0.326 -0.4 -1.3, 0.4 0.336
Antibiotics use between 0-12 months old









    No 232 (69%)


    Yes 105 (31%) -0.1 -0.8, 0.6 0.756 -0.1 -0.8, 0.6 0.822 -0.1 -0.8, 0.6 0.851
Learning materials score at 3 years of age (HOME questionnaire) 309 0.0 -0.3, 0.2 0.798





Language stimulation score at 3 years of age (HOME questionnaire) 309 -0.3 -0.7, 0.1 0.143





Academic stimulation score at 3 years of age (HOME questionnaire) 309 0.1 -0.3, 0.4 0.711





Variety score at 3 years of age (HOME questionnaire) 309 0.0 -0.3, 0.3 0.903





HOME questionnaire total score 309 0.0 -0.1, 0.1 0.688 0.0 -0.1, 0.1 0.983 0.0 -0.1, 0.1 >0.999
Maternal anxiety score during the third trimester of pregnancy 329 0.1 0.0, 0.3 0.009





Maternal depression score during the third trimester of pregnancy 328 0.1 0.0, 0.2 0.186





Maternal anxiety and depression score during the third trimester of pregnancy 327 0.1 0.0, 0.2 0.014 0.1 0.0, 0.2 0.004 0.1 0.0, 0.2 0.002
Maternal anxiety score when child is one year old 265 0.2 0.1, 0.3 <0.001





Maternal depression score when child is one year old 265 0.2 0.1, 0.4 <0.001





Maternal anxiety and depression score when child is one year old 265 0.2 0.1, 0.2 <0.001





Maternal active smoking during pregnancy









    No 295 (94%)


    Yes 19 (6.1%) -0.6 -1.9, 0.7 0.348 -0.3 -2.7, 2.0 0.753 -0.3 -2.7, 2.0 0.751
Maternal passive smoking during pregnancy









    No 266 (82%)






    Yes 57 (18%) -0.1 -0.9, 0.7 0.786





Child passive smoking during the first year of life









    No 262 (78%)






    Yes 76 (22%) -0.2 -0.9, 0.6 0.691





Child perinatal exposure to tabacco up to one year









    No 214 (66%)






    Yes 108 (34%) 0.0 -0.7, 0.6 0.921





Child perinatal passive smoking up to one year









    No 221 (68%)


    Yes 105 (32%) 0.0 -0.7, 0.7 0.996 -0.1 -0.9, 0.7 0.839 -0.1 -0.9, 0.7 0.778
Maternal alcohol consumption during pregnancy









    Did not drink 102 (30%)






    Drank only before finding out she was pregnant 162 (48%) -0.4 -1.2, 0.3 0.237





    Drank 72 (21%) -0.8 -1.7, 0.1 0.091





Maternal alcohol consumption during pregnancy









    Did not drink 102 (30%)






    Drank only before finding out she was pregnant 162 (48%) -0.4 -1.2, 0.3 0.237





    <1drink/month when she knew she was pregnant 61 (18%) -0.9 -1.8, 0.1 0.074





    >1drink/month when she knew she was pregnant 11 (3.3%) -0.3 -2.1, 1.5 0.754





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 201 (63%)






    Other 119 (37%) 0.8 0.1, 1.4 0.020





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 263 (82%)




    Other 57 (18%) 0.9 0.0, 1.7 0.045 1.0 0.1, 1.9 0.027


Main mode of child care up to 1 year









    Collective day care 270 (84%)




    Other 50 (16%) 0.7 -0.2, 1.6 0.129


0.8 -0.1, 1.8 0.096
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 58 (18%)






    Nursery assistant (out child home) 143 (45%) 0.2 -0.7, 1.1 0.620





    Other 119 (37%) 0.9 0.0, 1.9 0.043





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 98 (31%)






    Nursery assistant (out child home) 165 (52%) 0.3 -0.4, 1.0 0.411





    Other 57 (18%) 1.0 0.1, 2.0 0.032





Main mode of child care up to 1 year









    Collective day care 101 (32%)






    Nursery assistant (out child home) 169 (53%) 0.4 -0.3, 1.1 0.308





    Other 50 (16%) 0.9 -0.1, 1.9 0.069





Paternal education









    ≥5 years after graduation 152 (64%)






    3-4 years after graduation 41 (17%) 0.1 -1.0, 1.1 0.902





    2 years or less after graduation 45 (19%) 0.2 -0.8, 1.2 0.688





Paternal age at child birth (years) 303 0.0 -0.1, 0.0 0.338





Paternal age at child birth









    23-31 years 99 (33%)






    32-36 years 102 (34%) -0.9 -1.7, -0.1 0.028





    37-72 years 102 (34%) -0.3 -1.1, 0.5 0.437





Child age at the SRS 3 years evaluation 338 0.0 0.0, 0.1 0.324





Child age at the SRS 3 years evaluation



0.0 0.0, 0.1 0.308 0.0 0.0, 0.1 0.291
No. Obs.



338

338





0.098

0.092

Adjusted R²



0.026

0.019

1 N; n (%)
2 CI = Confidence Interval
Figure 68: Multivariate model hypothesis checking (outcome is BRIEF-P shift score Y3, before inclusion of microbiota variables)

Emotional control score Y3

Table 12:

Influence of maternal and child characteristics on the BRIEF-P emotional control score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3371 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 337 0.2 -0.6, 1.0 0.667





Birth weight









    <3 Kg 70 (21%)


    3-3.4 Kg 165 (49%) 0.2 -0.8, 1.2 0.707 0.0 -1.2, 1.1 0.945 0.0 -1.2, 1.2 0.972
    ≥3.5 Kg 102 (30%) 0.4 -0.7, 1.4 0.506 0.2 -1.3, 1.7 0.817 0.2 -1.3, 1.7 0.797
Birth length (cm) 336 0.0 -0.2, 0.1 0.763





Birth length









    <50 cm 121 (36%)


    50-51 cm 134 (40%) 0.3 -0.6, 1.1 0.525 0.2 -0.8, 1.2 0.706 0.2 -0.8, 1.2 0.698
    ≥52 cm 81 (24%) 0.4 -0.6, 1.3 0.463 0.3 -1.0, 1.7 0.632 0.3 -1.0, 1.7 0.638
Weight at one year (Kg) 333 0.0 -0.3, 0.4 0.789





Weight at one year









    <8.5 Kg 58 (17%)






    8.5-9.9 Kg 182 (55%) 0.7 -0.4, 1.7 0.204





    ≥10 Kg 93 (28%) 0.8 -0.3, 1.9 0.166





Length at one year (cm) 326 0.0 -0.1, 0.2 0.502





Length at one year









    <75 cm 119 (37%)






    75-77.9 cm 116 (36%) 0.4 -0.5, 1.3 0.364





    ≥78 cm 91 (28%) 0.6 -0.3, 1.6 0.192





Weight at 3 years (Kg) 312 0.1 -0.2, 0.3 0.620





Weight at 3 years









    9-13 Kg 105 (34%)






    14 Kg 104 (33%) 0.0 -1.0, 0.9 0.942





    15-20 Kg 103 (33%) 0.4 -0.6, 1.3 0.444





Length at 3 years (cm) 310 0.1 0.0, 0.2 0.234





Length at 3 years









    81-93 cm 95 (31%)






    94-95 cm 108 (35%) 0.5 -0.5, 1.4 0.337





    96-106 cm 107 (35%) 0.6 -0.4, 1.5 0.236





Child sex









    Male 180 (53%)


    Female 157 (47%) 0.0 -0.8, 0.7 0.925 0.2 -0.6, 1.0 0.636 0.2 -0.6, 1.0 0.617
Maternal education









    ≥5 years after graduation 194 (58%)






    3-4 years after graduation 90 (27%) 0.7 -0.1, 1.6 0.098





    2 years or less after graduation 51 (15%) -0.2 -1.3, 0.9 0.724





Maternal education









    ≥5 years after graduation 194 (58%)


    <5 years after graduation 141 (42%) 0.4 -0.4, 1.1 0.300 0.4 -0.4, 1.2 0.283 0.4 -0.3, 1.2 0.271
Maternal age at conception (years) 337 -0.1 -0.2, 0.0 0.048 -0.1 -0.2, 0.0 0.166 -0.1 -0.2, 0.0 0.175
Maternal BMI before pregnancy (kg/m2) 336 0.0 -0.1, 0.1 0.863





Maternal BMI before pregnancy









    <19 Kg/m2 46 (14%)


    19-23.9 Kg/m2 212 (63%) 0.5 -0.6, 1.6 0.381 0.7 -0.4, 1.8 0.211 0.7 -0.4, 1.8 0.223
    ≥24 Kg/m2 78 (23%) 0.2 -1.1, 1.5 0.746 0.3 -1.0, 1.6 0.699 0.3 -1.0, 1.6 0.701
Maternal parity









    None 153 (45%)


    1 child or more 184 (55%) -0.9 -1.6, -0.2 0.016 -1.2 -2.0, -0.3 0.007 -1.1 -2.0, -0.3 0.008
Breastfeeding duration









    Not breastfed 26 (7.9%)


    <24 weeks 115 (35%) -0.1 -1.6, 1.3 0.846 0.1 -1.4, 1.6 0.927 0.0 -1.5, 1.6 0.949
    24-47 weeks 111 (34%) 0.5 -1.0, 2.0 0.493 1.0 -0.6, 2.5 0.217 0.9 -0.6, 2.5 0.228
    Still breastfeed at 48 weeks 77 (23%) 0.7 -0.9, 2.2 0.379 1.0 -0.6, 2.6 0.218 1.0 -0.6, 2.6 0.215
Gestational duration, completed weeks 337 0.1 -0.1, 0.3 0.475 0.1 -0.2, 0.3 0.675 0.1 -0.2, 0.3 0.703
Delivery mode









    Vaginal delivery 282 (84%)


    C-section 55 (16%) 0.2 -0.8, 1.2 0.767 0.0 -1.0, 1.1 0.945 0.0 -1.0, 1.1 0.978
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 243 (79%)


    Between 6 and 12 months old 48 (16%) -0.1 -1.2, 0.9 0.786 -0.4 -1.6, 0.7 0.476 -0.4 -1.6, 0.8 0.488
    Not introduced at 12 months old 15 (4.9%) 1.1 -0.7, 2.9 0.236 1.3 -0.6, 3.2 0.175 1.4 -0.6, 3.3 0.165
Presence of pets









    No 215 (72%)


    One or more 84 (28%) 0.4 -0.4, 1.3 0.305 0.2 -0.8, 1.1 0.746 0.2 -0.8, 1.1 0.723
Antibiotics use between 0-12 months old









    No 232 (69%)


    Yes 104 (31%) -0.1 -0.9, 0.7 0.835 0.1 -0.8, 0.9 0.849 0.1 -0.8, 0.9 0.852
Learning materials score at 3 years of age (HOME questionnaire) 308 -0.1 -0.4, 0.2 0.581





Language stimulation score at 3 years of age (HOME questionnaire) 308 -0.4 -0.8, 0.1 0.102





Academic stimulation score at 3 years of age (HOME questionnaire) 308 0.1 -0.3, 0.5 0.667





Variety score at 3 years of age (HOME questionnaire) 308 -0.1 -0.4, 0.3 0.738





HOME questionnaire total score 308 -0.1 -0.2, 0.1 0.440 0.0 -0.2, 0.1 0.633 0.0 -0.2, 0.1 0.640
Maternal anxiety score during the third trimester of pregnancy 328 0.1 0.0, 0.3 0.036





Maternal depression score during the third trimester of pregnancy 328 0.1 -0.1, 0.2 0.218





Maternal anxiety and depression score during the third trimester of pregnancy 327 0.1 0.0, 0.2 0.037 0.1 0.0, 0.2 0.008 0.1 0.0, 0.2 0.007
Maternal anxiety score when child is one year old 265 0.2 0.0, 0.3 0.020





Maternal depression score when child is one year old 265 0.3 0.1, 0.4 <0.001





Maternal anxiety and depression score when child is one year old 265 0.2 0.1, 0.2 <0.001





Maternal active smoking during pregnancy









    No 295 (94%)


    Yes 19 (6.1%) 0.0 -1.6, 1.6 0.997 0.1 -2.0, 2.3 0.893 0.1 -2.0, 2.2 0.901
Maternal passive smoking during pregnancy









    No 266 (82%)






    Yes 57 (18%) 0.2 -0.8, 1.2 0.674





Child passive smoking during the first year of life









    No 261 (77%)






    Yes 76 (23%) 0.2 -0.7, 1.1 0.646





Child perinatal exposure to tabacco up to one year









    No 214 (66%)






    Yes 108 (34%) 0.2 -0.5, 1.0 0.544





Child perinatal passive smoking up to one year









    No 221 (68%)


    Yes 105 (32%) 0.3 -0.5, 1.1 0.455 0.1 -0.8, 0.9 0.850 0.1 -0.8, 0.9 0.849
Maternal alcohol consumption during pregnancy









    Did not drink 101 (30%)






    Drank only before finding out she was pregnant 162 (48%) 0.1 -0.8, 0.9 0.869





    Drank 72 (21%) -0.5 -1.5, 0.6 0.397





Maternal alcohol consumption during pregnancy









    Did not drink 101 (30%)






    Drank only before finding out she was pregnant 162 (48%) 0.1 -0.8, 0.9 0.869





    <1drink/month when she knew she was pregnant 61 (18%) -0.4 -1.5, 0.7 0.459





    >1drink/month when she knew she was pregnant 11 (3.3%) -0.7 -2.8, 1.5 0.552





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 200 (63%)






    Other 119 (37%) 0.0 -0.8, 0.8 0.961





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 262 (82%)




    Other 57 (18%) 0.0 -1.0, 1.0 0.979 0.1 -0.9, 1.2 0.809


Main mode of child care up to 1 year









    Collective day care 269 (84%)




    Other 50 (16%) -0.3 -1.3, 0.8 0.624


-0.1 -1.2, 1.0 0.830
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 58 (18%)






    Nursery assistant (out child home) 142 (45%) 1.1 0.0, 2.2 0.046





    Other 119 (37%) 0.8 -0.3, 1.8 0.179





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 98 (31%)






    Nursery assistant (out child home) 164 (51%) 0.7 -0.2, 1.6 0.115





    Other 57 (18%) 0.4 -0.7, 1.6 0.463





Main mode of child care up to 1 year









    Collective day care 101 (32%)






    Nursery assistant (out child home) 168 (53%) 0.6 -0.3, 1.5 0.182





    Other 50 (16%) 0.1 -1.1, 1.3 0.865





Paternal education









    ≥5 years after graduation 152 (64%)






    3-4 years after graduation 41 (17%) 0.3 -0.9, 1.5 0.629





    2 years or less after graduation 45 (19%) 0.2 -0.9, 1.4 0.686





Paternal age at child birth (years) 302 -0.1 -0.2, 0.0 0.006





Paternal age at child birth









    23-31 years 99 (33%)






    32-36 years 101 (33%) -1.3 -2.3, -0.4 0.007





    37-72 years 102 (34%) -1.5 -2.5, -0.6 0.002





Child age at the SRS 3 years evaluation 337 0.0 -0.1, 0.1 0.923





Child age at the SRS 3 years evaluation



0.0 -0.1, 0.1 0.802 0.0 -0.1, 0.1 0.801
No. Obs.



337

337





0.087

0.087

Adjusted R²



0.013

0.013

1 N; n (%)
2 CI = Confidence Interval
Figure 69: Multivariate model hypothesis checking (outcome is BRIEF-P emotional control score Y3, before inclusion of microbiota variables)

Working memory score Y3

Table 13:

Influence of maternal and child characteristics on the BRIEF-P working memory score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3291 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 329 0.1 -0.9, 1.1 0.843





Birth weight









    <3 Kg 69 (21%)


    3-3.4 Kg 162 (49%) -1.0 -2.2, 0.2 0.114 -1.4 -2.9, 0.1 0.061 -1.5 -2.9, 0.0 0.050
    ≥3.5 Kg 98 (30%) -0.5 -1.8, 0.8 0.468 -0.7 -2.6, 1.1 0.437 -0.8 -2.7, 1.1 0.400
Birth length (cm) 328 -0.1 -0.3, 0.1 0.332





Birth length









    <50 cm 118 (36%)


    50-51 cm 131 (40%) -0.1 -1.2, 1.0 0.848 -0.2 -1.5, 1.0 0.720 -0.2 -1.5, 1.0 0.711
    ≥52 cm 79 (24%) -0.2 -1.4, 1.1 0.808 -0.5 -2.2, 1.2 0.568 -0.5 -2.2, 1.2 0.596
Weight at one year (Kg) 325 -0.1 -0.6, 0.3 0.631





Weight at one year









    <8.5 Kg 56 (17%)






    8.5-9.9 Kg 177 (54%) 0.1 -1.2, 1.5 0.831





    ≥10 Kg 92 (28%) 0.7 -0.7, 2.2 0.332





Length at one year (cm) 318 0.0 -0.2, 0.1 0.648





Length at one year









    <75 cm 117 (37%)






    75-77.9 cm 111 (35%) -0.8 -2.0, 0.3 0.148





    ≥78 cm 90 (28%) 0.5 -0.7, 1.7 0.404





Weight at 3 years (Kg) 304 0.1 -0.2, 0.4 0.576





Weight at 3 years









    9-13 Kg 102 (34%)






    14 Kg 99 (33%) 0.3 -0.9, 1.5 0.639





    15-20 Kg 103 (34%) 0.6 -0.6, 1.8 0.316





Length at 3 years (cm) 302 0.0 -0.1, 0.1 0.906





Length at 3 years









    81-93 cm 92 (30%)






    94-95 cm 107 (35%) -0.6 -1.8, 0.5 0.289





    96-106 cm 103 (34%) 0.3 -0.9, 1.5 0.578





Child sex









    Male 177 (54%)


    Female 152 (46%) -0.1 -1.0, 0.9 0.908 -0.2 -1.2, 0.8 0.738 -0.2 -1.2, 0.8 0.734
Maternal education









    ≥5 years after graduation 192 (59%)






    3-4 years after graduation 87 (27%) 0.9 -0.2, 2.0 0.102





    2 years or less after graduation 48 (15%) 0.7 -0.7, 2.1 0.320





Maternal education









    ≥5 years after graduation 192 (59%)


    <5 years after graduation 135 (41%) 0.8 -0.1, 1.8 0.085 0.9 0.0, 1.9 0.061 0.9 0.0, 1.9 0.062
Maternal age at conception (years) 329 0.0 -0.2, 0.1 0.553 0.0 -0.1, 0.1 0.865 0.0 -0.1, 0.1 0.856
Maternal BMI before pregnancy (kg/m2) 328 0.0 -0.2, 0.1 0.478





Maternal BMI before pregnancy









    <19 Kg/m2 45 (14%)


    19-23.9 Kg/m2 207 (63%) 0.7 -0.7, 2.1 0.341 0.9 -0.5, 2.4 0.192 1.0 -0.4, 2.4 0.179
    ≥24 Kg/m2 76 (23%) -0.3 -1.9, 1.3 0.705 -0.1 -1.7, 1.5 0.915 -0.1 -1.7, 1.5 0.902
Maternal parity









    None 152 (46%)


    1 child or more 177 (54%) -1.2 -2.1, -0.3 0.012 -1.4 -2.4, -0.3 0.009 -1.4 -2.5, -0.4 0.007
Breastfeeding duration









    Not breastfed 25 (7.8%)


    <24 weeks 113 (35%) 0.5 -1.5, 2.4 0.643 0.7 -1.2, 2.7 0.460 0.7 -1.2, 2.7 0.457
    24-47 weeks 110 (34%) 0.5 -1.4, 2.5 0.580 1.3 -0.7, 3.2 0.203 1.3 -0.7, 3.2 0.197
    Still breastfeed at 48 weeks 73 (23%) 0.5 -1.5, 2.5 0.626 1.2 -0.8, 3.2 0.232 1.2 -0.8, 3.2 0.245
Gestational duration, completed weeks 329 0.1 -0.2, 0.4 0.352 0.3 -0.1, 0.6 0.112 0.3 -0.1, 0.6 0.095
Delivery mode









    Vaginal delivery 274 (83%)


    C-section 55 (17%) 0.2 -1.1, 1.4 0.780 -0.2 -1.5, 1.1 0.781 -0.1 -1.5, 1.2 0.834
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 235 (79%)


    Between 6 and 12 months old 49 (16%) -0.3 -1.7, 1.0 0.626 -0.9 -2.2, 0.4 0.171 -0.9 -2.3, 0.4 0.161
    Not introduced at 12 months old 14 (4.7%) 1.4 -0.9, 3.7 0.237 1.4 -1.2, 4.1 0.291 1.4 -1.3, 4.1 0.305
Presence of pets









    No 208 (72%)


    One or more 82 (28%) -0.8 -1.8, 0.3 0.159 -0.9 -2.0, 0.2 0.128 -0.9 -2.0, 0.2 0.119
Antibiotics use between 0-12 months old









    No 224 (68%)


    Yes 104 (32%) 0.2 -0.8, 1.2 0.728 0.4 -0.6, 1.5 0.418 0.4 -0.6, 1.5 0.426
Learning materials score at 3 years of age (HOME questionnaire) 300 -0.4 -0.8, -0.1 0.017





Language stimulation score at 3 years of age (HOME questionnaire) 300 0.1 -0.5, 0.7 0.704





Academic stimulation score at 3 years of age (HOME questionnaire) 300 0.1 -0.4, 0.7 0.596





Variety score at 3 years of age (HOME questionnaire) 300 -0.5 -0.9, -0.1 0.024





HOME questionnaire total score 300 -0.2 -0.4, 0.0 0.062 -0.1 -0.3, 0.1 0.211 -0.1 -0.3, 0.1 0.202
Maternal anxiety score during the third trimester of pregnancy 320 0.1 0.0, 0.3 0.110





Maternal depression score during the third trimester of pregnancy 319 0.1 -0.1, 0.3 0.244





Maternal anxiety and depression score during the third trimester of pregnancy 318 0.1 0.0, 0.2 0.102 0.1 0.0, 0.2 0.015 0.1 0.0, 0.2 0.019
Maternal anxiety score when child is one year old 258 0.1 -0.1, 0.2 0.390





Maternal depression score when child is one year old 258 0.1 -0.1, 0.3 0.354





Maternal anxiety and depression score when child is one year old 258 0.1 0.0, 0.2 0.279





Maternal active smoking during pregnancy









    No 287 (94%)


    Yes 18 (5.9%) 0.6 -1.4, 2.6 0.556 -0.3 -2.6, 2.1 0.806 -0.3 -2.6, 2.1 0.827
Maternal passive smoking during pregnancy









    No 259 (82%)






    Yes 55 (18%) 1.0 -0.2, 2.3 0.097





Child passive smoking during the first year of life









    No 254 (77%)






    Yes 75 (23%) 0.5 -0.6, 1.6 0.377





Child perinatal exposure to tabacco up to one year









    No 207 (66%)






    Yes 106 (34%) 1.1 0.1, 2.1 0.029





Child perinatal passive smoking up to one year









    No 214 (68%)


    Yes 103 (32%) 1.2 0.2, 2.1 0.024 0.9 -0.4, 2.1 0.177 0.9 -0.4, 2.2 0.166
Maternal alcohol consumption during pregnancy









    Did not drink 100 (31%)






    Drank only before finding out she was pregnant 157 (48%) -0.3 -1.4, 0.8 0.604





    Drank 70 (21%) -0.2 -1.6, 1.1 0.738





Maternal alcohol consumption during pregnancy









    Did not drink 100 (31%)






    Drank only before finding out she was pregnant 157 (48%) -0.3 -1.4, 0.8 0.604





    <1drink/month when she knew she was pregnant 61 (19%) -0.4 -1.8, 1.0 0.552





    >1drink/month when she knew she was pregnant 9 (2.8%) 1.1 -1.9, 4.1 0.475





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 197 (63%)






    Other 114 (37%) -0.3 -1.3, 0.7 0.517





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 256 (82%)




    Other 55 (18%) -1.3 -2.6, 0.0 0.045 -0.8 -2.1, 0.6 0.263


Main mode of child care up to 1 year









    Collective day care 263 (85%)




    Other 48 (15%) -1.0 -2.3, 0.4 0.152


-0.3 -1.8, 1.1 0.662
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 58 (19%)






    Nursery assistant (out child home) 139 (45%) 0.4 -0.9, 1.8 0.528





    Other 114 (37%) 0.0 -1.4, 1.4 0.968





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 96 (31%)






    Nursery assistant (out child home) 160 (51%) -0.2 -1.3, 0.9 0.726





    Other 55 (18%) -1.4 -2.9, 0.0 0.054





Main mode of child care up to 1 year









    Collective day care 99 (32%)






    Nursery assistant (out child home) 164 (53%) -0.2 -1.3, 0.9 0.701





    Other 48 (15%) -1.1 -2.6, 0.4 0.147





Paternal education









    ≥5 years after graduation 151 (65%)






    3-4 years after graduation 39 (17%) 0.9 -0.6, 2.5 0.246





    2 years or less after graduation 42 (18%) -0.2 -1.8, 1.3 0.752





Paternal age at child birth (years) 296 -0.1 -0.2, 0.0 0.289





Paternal age at child birth









    23-31 years 96 (32%)






    32-36 years 100 (34%) -0.5 -1.8, 0.7 0.383





    37-72 years 100 (34%) -1.0 -2.2, 0.3 0.120





Child age at the SRS 3 years evaluation 329 0.1 0.0, 0.2 0.234





Child age at the SRS 3 years evaluation



0.1 0.0, 0.2 0.232 0.1 0.0, 0.2 0.236
No. Obs.



329

329





0.124

0.121

Adjusted R²



0.052

0.048

1 N; n (%)
2 CI = Confidence Interval
Figure 70: Multivariate model hypothesis checking (outcome is BRIEF-P working memory score Y3, before inclusion of microbiota variables)

Plan/organization score Y3

Table 14:

Influence of maternal and child characteristics on the BRIEF-P plan and organization score at 2 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3351 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 335 0.1 -0.6, 0.7 0.866





Birth weight









    <3 Kg 70 (21%)


    3-3.4 Kg 165 (49%) -0.2 -0.9, 0.6 0.678 -0.3 -1.2, 0.6 0.536 -0.3 -1.2, 0.6 0.518
    ≥3.5 Kg 100 (30%) -0.1 -0.9, 0.8 0.893 -0.2 -1.4, 1.0 0.728 -0.2 -1.4, 1.0 0.711
Birth length (cm) 334 0.0 -0.1, 0.1 0.904





Birth length









    <50 cm 121 (36%)


    50-51 cm 135 (40%) -0.1 -0.8, 0.6 0.745 -0.2 -1.1, 0.6 0.557 -0.2 -1.0, 0.6 0.564
    ≥52 cm 78 (23%) 0.2 -0.6, 1.0 0.567 0.2 -0.9, 1.3 0.767 0.2 -0.9, 1.3 0.749
Weight at one year (Kg) 331 0.0 -0.3, 0.3 0.875





Weight at one year









    <8.5 Kg 58 (18%)






    8.5-9.9 Kg 181 (55%) 0.5 -0.3, 1.4 0.201





    ≥10 Kg 92 (28%) 0.8 -0.2, 1.7 0.102





Length at one year (cm) 324 0.0 -0.1, 0.1 0.882





Length at one year









    <75 cm 119 (37%)






    75-77.9 cm 113 (35%) -0.5 -1.2, 0.2 0.157





    ≥78 cm 92 (28%) 0.0 -0.8, 0.8 0.985





Weight at 3 years (Kg) 310 0.1 -0.1, 0.3 0.296





Weight at 3 years









    9-13 Kg 105 (34%)






    14 Kg 103 (33%) 0.3 -0.4, 1.1 0.418





    15-20 Kg 102 (33%) 0.3 -0.5, 1.1 0.418





Length at 3 years (cm) 308 0.1 0.0, 0.1 0.219





Length at 3 years









    81-93 cm 95 (31%)






    94-95 cm 108 (35%) -0.1 -0.8, 0.7 0.844





    96-106 cm 105 (34%) 0.5 -0.3, 1.2 0.233





Child sex









    Male 179 (53%)


    Female 156 (47%) -0.2 -0.8, 0.4 0.416 -0.2 -0.8, 0.5 0.558 -0.2 -0.8, 0.5 0.575
Maternal education









    ≥5 years after graduation 193 (58%)






    3-4 years after graduation 89 (27%) 0.9 0.2, 1.6 0.008





    2 years or less after graduation 51 (15%) 0.6 -0.3, 1.4 0.175





Maternal education









    ≥5 years after graduation 193 (58%)


    <5 years after graduation 140 (42%) 0.8 0.2, 1.4 0.008 0.9 0.3, 1.6 0.003 0.9 0.3, 1.6 0.003
Maternal age at conception (years) 335 0.0 -0.1, 0.0 0.209 0.0 -0.1, 0.1 0.470 0.0 -0.1, 0.1 0.483
Maternal BMI before pregnancy (kg/m2) 334 0.0 -0.1, 0.1 0.833





Maternal BMI before pregnancy









    <19 Kg/m2 46 (14%)


    19-23.9 Kg/m2 212 (63%) 0.0 -0.9, 0.9 0.950 0.0 -0.9, 0.9 0.938 0.0 -0.9, 0.9 0.947
    ≥24 Kg/m2 76 (23%) -0.2 -1.3, 0.8 0.663 -0.3 -1.3, 0.8 0.613 -0.3 -1.3, 0.8 0.601
Maternal parity









    None 153 (46%)


    1 child or more 182 (54%) -0.5 -1.1, 0.1 0.086 -0.7 -1.3, 0.0 0.050 -0.7 -1.3, 0.0 0.052
Breastfeeding duration









    Not breastfed 26 (8.0%)


    <24 weeks 114 (35%) -0.4 -1.6, 0.8 0.509 -0.2 -1.4, 1.0 0.719 -0.2 -1.4, 1.0 0.705
    24-47 weeks 111 (34%) 0.2 -1.0, 1.3 0.797 0.6 -0.7, 1.9 0.369 0.6 -0.7, 1.9 0.376
    Still breastfeed at 48 weeks 76 (23%) -0.1 -1.4, 1.1 0.838 0.3 -1.0, 1.6 0.651 0.3 -1.0, 1.6 0.660
Gestational duration, completed weeks 335 0.0 -0.2, 0.2 0.841 0.1 -0.2, 0.3 0.603 0.1 -0.2, 0.3 0.598
Delivery mode









    Vaginal delivery 281 (84%)


    C-section 54 (16%) 0.1 -0.7, 1.0 0.733 -0.1 -1.0, 0.8 0.804 -0.1 -1.0, 0.8 0.810
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 241 (79%)


    Between 6 and 12 months old 49 (16%) 0.0 -0.9, 0.9 0.977 -0.4 -1.3, 0.5 0.351 -0.4 -1.3, 0.5 0.349
    Not introduced at 12 months old 15 (4.9%) 1.6 0.1, 3.0 0.037 1.6 0.1, 3.1 0.040 1.6 0.1, 3.1 0.038
Presence of pets









    No 213 (72%)


    One or more 84 (28%) -0.3 -1.0, 0.4 0.368 -0.5 -1.2, 0.2 0.184 -0.5 -1.2, 0.2 0.187
Antibiotics use between 0-12 months old









    No 232 (69%)


    Yes 102 (31%) 0.1 -0.5, 0.8 0.727 0.2 -0.5, 0.8 0.614 0.2 -0.5, 0.8 0.622
Learning materials score at 3 years of age (HOME questionnaire) 306 0.0 -0.2, 0.3 0.689





Language stimulation score at 3 years of age (HOME questionnaire) 306 0.0 -0.4, 0.4 0.870





Academic stimulation score at 3 years of age (HOME questionnaire) 306 0.1 -0.2, 0.5 0.533





Variety score at 3 years of age (HOME questionnaire) 306 -0.1 -0.3, 0.2 0.692





HOME questionnaire total score 306 0.0 -0.1, 0.1 0.769 0.1 -0.1, 0.2 0.402 0.1 -0.1, 0.2 0.403
Maternal anxiety score during the third trimester of pregnancy 326 0.1 0.0, 0.2 0.108





Maternal depression score during the third trimester of pregnancy 325 0.1 0.0, 0.2 0.091





Maternal anxiety and depression score during the third trimester of pregnancy 324 0.1 0.0, 0.1 0.042 0.1 0.0, 0.2 0.013 0.1 0.0, 0.2 0.014
Maternal anxiety score when child is one year old 263 0.1 0.0, 0.2 0.107





Maternal depression score when child is one year old 263 0.1 -0.1, 0.2 0.373





Maternal anxiety and depression score when child is one year old 263 0.1 0.0, 0.1 0.123





Maternal active smoking during pregnancy









    No 293 (94%)


    Yes 19 (6.1%) -0.1 -1.4, 1.2 0.922 -0.4 -1.8, 0.9 0.539 -0.4 -1.8, 0.9 0.541
Maternal passive smoking during pregnancy









    No 264 (82%)






    Yes 57 (18%) -0.1 -0.9, 0.7 0.890





Child passive smoking during the first year of life









    No 261 (78%)






    Yes 74 (22%) 0.6 -0.1, 1.3 0.120





Child perinatal exposure to tabacco up to one year









    No 214 (67%)






    Yes 106 (33%) 0.4 -0.3, 1.0 0.251





Child perinatal passive smoking up to one year









    No 221 (68%)


    Yes 103 (32%) 0.5 -0.2, 1.1 0.159 0.4 -0.3, 1.2 0.255 0.4 -0.3, 1.2 0.245
Maternal alcohol consumption during pregnancy









    Did not drink 101 (30%)






    Drank only before finding out she was pregnant 161 (48%) 0.1 -0.6, 0.8 0.729





    Drank 71 (21%) 0.3 -0.5, 1.2 0.460





Maternal alcohol consumption during pregnancy









    Did not drink 101 (30%)






    Drank only before finding out she was pregnant 161 (48%) 0.1 -0.6, 0.8 0.729





    <1drink/month when she knew she was pregnant 60 (18%) 0.3 -0.6, 1.2 0.564





    >1drink/month when she knew she was pregnant 11 (3.3%) 0.6 -1.1, 2.4 0.481





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 200 (63%)






    Other 118 (37%) -0.2 -0.9, 0.4 0.454





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 261 (82%)




    Other 57 (18%) -0.3 -1.1, 0.5 0.466 -0.2 -1.1, 0.6 0.592


Main mode of child care up to 1 year









    Collective day care 268 (84%)




    Other 50 (16%) -0.3 -1.1, 0.5 0.484


-0.2 -1.1, 0.6 0.597
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 58 (18%)






    Nursery assistant (out child home) 142 (45%) 0.6 -0.3, 1.4 0.196





    Other 118 (37%) 0.2 -0.7, 1.0 0.726





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 98 (31%)






    Nursery assistant (out child home) 163 (51%) 0.1 -0.6, 0.8 0.762





    Other 57 (18%) -0.2 -1.1, 0.7 0.621





Main mode of child care up to 1 year









    Collective day care 101 (32%)






    Nursery assistant (out child home) 167 (53%) 0.1 -0.6, 0.8 0.743





    Other 50 (16%) -0.2 -1.2, 0.7 0.635





Paternal education









    ≥5 years after graduation 150 (64%)






    3-4 years after graduation 41 (17%) 0.1 -0.9, 1.1 0.823





    2 years or less after graduation 45 (19%) -0.3 -1.3, 0.6 0.490





Paternal age at child birth (years) 301 0.0 -0.1, 0.0 0.157





Paternal age at child birth









    23-31 years 98 (33%)






    32-36 years 101 (34%) -0.6 -1.4, 0.1 0.098





    37-72 years 102 (34%) -0.9 -1.6, -0.1 0.027





Child age at the SRS 3 years evaluation 335 0.0 0.0, 0.1 0.208





Child age at the SRS 3 years evaluation



0.0 0.0, 0.1 0.311 0.0 0.0, 0.1 0.316
No. Obs.



335

335





0.107

0.107

Adjusted R²



0.035

0.035

1 N; n (%)
2 CI = Confidence Interval
Figure 71: Multivariate model hypothesis checking (outcome is BRIEF-P plan and organization score Y3, before inclusion of microbiota variables)

IQ Y3

IQ verbal comprehension score Y3

Table 15:

Influence of maternal and child characteristics on the IQ verbal comprehension score at 3 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 315 -2.0 -4.8, 0.9 0.175





Birth weight









    <3 Kg 63 (20%)


    3-3.4 Kg 159 (50%) -0.7 -4.1, 2.7 0.697 1.9 -2.1, 5.9 0.357 1.7 -2.3, 5.7 0.409
    ≥3.5 Kg 93 (30%) -0.9 -4.7, 2.8 0.619 2.1 -3.1, 7.3 0.421 2.0 -3.2, 7.1 0.451
Birth length (cm) 314 -0.2 -0.8, 0.4 0.532





Birth length









    <50 cm 116 (37%)


    50-51 cm 124 (39%) -2.0 -4.9, 1.0 0.191 -2.1 -5.6, 1.4 0.249 -2.0 -5.5, 1.5 0.264
    ≥52 cm 74 (24%) -1.1 -4.5, 2.2 0.504 -0.4 -5.0, 4.2 0.868 -0.3 -4.9, 4.4 0.907
Weight at one year (Kg) 312 -0.6 -1.9, 0.6 0.316





Weight at one year









    <8.5 Kg 56 (18%)






    8.5-9.9 Kg 174 (56%) -1.3 -4.7, 2.2 0.474





    ≥10 Kg 82 (26%) -1.3 -5.2, 2.6 0.512





Length at one year (cm) 306 -0.4 -0.8, 0.1 0.109





Length at one year









    <75 cm 116 (38%)






    75-77.9 cm 109 (36%) -3.4 -6.4, -0.4 0.025





    ≥78 cm 81 (26%) -2.0 -5.2, 1.3 0.232





Weight at 3 years (Kg) 314 0.1 -0.7, 0.9 0.858





Weight at 3 years









    9-13 Kg 104 (33%)






    14 Kg 106 (34%) -1.5 -4.6, 1.6 0.349





    15-20 Kg 104 (33%) -0.1 -3.2, 3.1 0.957





Length at 3 years (cm) 312 0.1 -0.3, 0.4 0.663





Length at 3 years









    81-93 cm 95 (30%)






    94-95 cm 109 (35%) -0.5 -3.6, 2.7 0.774





    96-106 cm 108 (35%) 1.1 -2.1, 4.2 0.500





Child sex









    Male 167 (53%)


    Female 148 (47%) 2.6 0.0, 5.1 0.046 1.5 -1.3, 4.2 0.293 1.5 -1.2, 4.3 0.279
Maternal education









    ≥5 years after graduation 182 (58%)






    3-4 years after graduation 86 (27%) -1.3 -4.3, 1.6 0.377





    2 years or less after graduation 45 (14%) -3.7 -7.5, 0.1 0.055





Maternal education









    ≥5 years after graduation 182 (58%)


    <5 years after graduation 131 (42%) -2.1 -4.7, 0.5 0.105 -1.5 -4.2, 1.1 0.255 -1.5 -4.2, 1.1 0.263
Maternal age at conception (years) 315 0.0 -0.4, 0.3 0.907 0.1 -0.3, 0.4 0.655 0.1 -0.3, 0.4 0.666
Maternal BMI before pregnancy (kg/m2) 314 0.0 -0.3, 0.4 0.939





Maternal BMI before pregnancy









    <19 Kg/m2 45 (14%)


    19-23.9 Kg/m2 198 (63%) 0.7 -3.0, 4.5 0.709 0.8 -3.0, 4.6 0.678 0.8 -3.0, 4.6 0.672
    ≥24 Kg/m2 71 (23%) 0.9 -3.4, 5.2 0.690 1.1 -3.3, 5.5 0.621 1.1 -3.4, 5.5 0.637
Maternal parity









    None 139 (44%)


    1 child or more 176 (56%) -3.3 -5.8, -0.7 0.012 -3.0 -5.8, -0.2 0.036 -3.1 -5.9, -0.3 0.031
Breastfeeding duration









    Not breastfed 25 (8.1%)


    <24 weeks 102 (33%) 0.7 -4.3, 5.8 0.779 -0.7 -5.8, 4.5 0.802 -0.7 -5.9, 4.5 0.787
    24-47 weeks 108 (35%) 2.4 -2.7, 7.4 0.353 1.0 -4.1, 6.1 0.692 1.0 -4.1, 6.1 0.701
    Still breastfeed at 48 weeks 72 (23%) 4.3 -1.0, 9.5 0.112 4.3 -1.1, 9.6 0.117 4.2 -1.1, 9.5 0.123
Gestational duration, completed weeks 315 -0.3 -1.2, 0.5 0.451 -0.4 -1.4, 0.6 0.418 -0.4 -1.4, 0.6 0.445
Delivery mode









    Vaginal delivery 263 (83%)


    C-section 52 (17%) -0.2 -3.7, 3.2 0.887 -1.2 -4.8, 2.4 0.507 -1.2 -4.7, 2.4 0.525
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 232 (80%)


    Between 6 and 12 months old 45 (16%) 1.0 -2.7, 4.7 0.593 1.3 -2.7, 5.3 0.514 1.3 -2.7, 5.2 0.528
    Not introduced at 12 months old 13 (4.5%) -7.6 -14.0, -1.2 0.021 -6.0 -12.5, 0.5 0.069 -5.9 -12.4, 0.6 0.075
Presence of pets









    No 203 (73%)


    One or more 77 (28%) 0.3 -2.7, 3.3 0.850 0.5 -2.8, 3.7 0.779 0.5 -2.7, 3.7 0.765
Antibiotics use between 0-12 months old









    No 212 (68%)


    Yes 102 (32%) -0.8 -3.6, 1.9 0.546 -0.7 -3.5, 2.1 0.631 -0.7 -3.5, 2.1 0.630
Learning materials score at 3 years of age (HOME questionnaire) 309 1.8 0.9, 2.8 <0.001





Language stimulation score at 3 years of age (HOME questionnaire) 309 1.1 -0.6, 2.7 0.199





Academic stimulation score at 3 years of age (HOME questionnaire) 309 1.9 0.5, 3.4 0.011





Variety score at 3 years of age (HOME questionnaire) 309 0.0 -1.2, 1.1 0.944





HOME questionnaire total score 309 0.8 0.3, 1.2 0.002 0.6 0.1, 1.1 0.021 0.6 0.1, 1.1 0.022
Maternal anxiety score during the third trimester of pregnancy 308 -0.3 -0.8, 0.1 0.161





Maternal depression score during the third trimester of pregnancy 307 -0.2 -0.7, 0.3 0.342





Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.2 -0.5, 0.1 0.176 -0.1 -0.4, 0.2 0.335 -0.2 -0.5, 0.1 0.285
Maternal anxiety score when child is one year old 254 -0.4 -0.9, 0.0 0.078





Maternal depression score when child is one year old 254 -0.3 -0.8, 0.2 0.293





Maternal anxiety and depression score when child is one year old 254 -0.3 -0.6, 0.0 0.086





Maternal active smoking during pregnancy









    No 272 (93%)


    Yes 19 (6.5%) -0.7 -6.1, 4.8 0.807 1.3 -4.9, 7.5 0.681 1.3 -4.9, 7.5 0.681
Maternal passive smoking during pregnancy









    No 248 (82%)






    Yes 54 (18%) -1.5 -4.8, 1.9 0.389





Child passive smoking during the first year of life









    No 240 (76%)






    Yes 75 (24%) -1.4 -4.4, 1.6 0.370





Child perinatal exposure to tabacco up to one year









    No 198 (66%)






    Yes 103 (34%) -1.6 -4.4, 1.2 0.256





Child perinatal passive smoking up to one year









    No 205 (67%)


    Yes 100 (33%) -1.2 -3.9, 1.6 0.407 -0.5 -3.5, 2.6 0.763 -0.4 -3.5, 2.7 0.792
Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) 1.7 -1.3, 4.6 0.267





    Drank 67 (21%) -1.9 -5.5, 1.7 0.293





Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) 1.7 -1.3, 4.6 0.266





    <1drink/month when she knew she was pregnant 58 (19%) -1.3 -5.1, 2.4 0.487





    >1drink/month when she knew she was pregnant 9 (2.9%) -5.8 -13.7, 2.1 0.149





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 183 (61%)






    Other 116 (39%) -1.3 -4.0, 1.3 0.328





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 246 (82%)




    Other 53 (18%) -3.0 -6.4, 0.4 0.081 -2.6 -6.3, 1.1 0.166


Main mode of child care up to 1 year









    Collective day care 251 (84%)




    Other 48 (16%) -2.7 -6.2, 0.9 0.143


-2.1 -5.9, 1.6 0.269
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 53 (18%)






    Nursery assistant (out child home) 130 (43%) 1.4 -2.3, 5.1 0.456





    Other 116 (39%) -0.3 -4.1, 3.4 0.858





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 94 (31%)






    Nursery assistant (out child home) 152 (51%) -0.8 -3.7, 2.2 0.609





    Other 53 (18%) -3.5 -7.4, 0.4 0.076





Main mode of child care up to 1 year









    Collective day care 96 (32%)






    Nursery assistant (out child home) 155 (52%) -0.8 -3.8, 2.1 0.579





    Other 48 (16%) -3.2 -7.2, 0.8 0.120





Paternal education









    ≥5 years after graduation 142 (63%)






    3-4 years after graduation 39 (17%) 1.0 -3.3, 5.2 0.652





    2 years or less after graduation 43 (19%) -2.3 -6.3, 1.8 0.277





Paternal age at child birth (years) 283 0.1 -0.2, 0.4 0.507





Paternal age at child birth









    23-31 years 90 (32%)






    32-36 years 94 (33%) 1.0 -2.4, 4.3 0.564





    37-72 years 99 (35%) -0.7 -4.0, 2.6 0.686





Child age at the IQ 3 years evaluation 315 0.3 0.0, 0.6 0.065





Child age at the IQ 3 years evaluation



0.3 0.0, 0.6 0.082 0.3 0.0, 0.6 0.082
No. Obs.



315

315





0.124

0.121

Adjusted R²



0.048

0.045

1 N; n (%)
2 CI = Confidence Interval
Figure 72: Multivariate model hypothesis checking (outcome is IQ verbal comprehension score Y3, before inclusion of microbiota variables)

IQ visuospacial score Y3

Table 16:

Influence of maternal and child characteristics on the IQ visuospatial score at 3 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 315 0.7 -2.0, 3.4 0.618





Birth weight









    <3 Kg 63 (20%)


    3-3.4 Kg 159 (50%) 1.3 -2.0, 4.5 0.452 0.6 -3.4, 4.6 0.786 0.3 -3.7, 4.3 0.895
    ≥3.5 Kg 93 (30%) 0.9 -2.7, 4.5 0.611 0.0 -5.1, 5.1 0.990 -0.2 -5.3, 5.0 0.952
Birth length (cm) 314 0.2 -0.4, 0.8 0.503





Birth length









    <50 cm 116 (37%)


    50-51 cm 124 (39%) 0.9 -1.9, 3.8 0.511 0.4 -3.0, 3.9 0.808 0.5 -3.0, 4.0 0.776
    ≥52 cm 74 (24%) 0.3 -2.9, 3.6 0.839 0.3 -4.2, 4.9 0.883 0.5 -4.1, 5.1 0.836
Weight at one year (Kg) 312 0.0 -1.2, 1.3 0.947





Weight at one year









    <8.5 Kg 56 (18%)






    8.5-9.9 Kg 174 (56%) 0.3 -3.1, 3.7 0.870





    ≥10 Kg 82 (26%) -0.2 -4.0, 3.6 0.921





Length at one year (cm) 306 0.0 -0.4, 0.4 0.975





Length at one year









    <75 cm 116 (38%)






    75-77.9 cm 109 (36%) -1.9 -4.8, 1.0 0.206





    ≥78 cm 81 (26%) -1.0 -4.2, 2.1 0.520





Weight at 3 years (Kg) 314 0.2 -0.6, 1.0 0.623





Weight at 3 years









    9-13 Kg 104 (33%)






    14 Kg 106 (34%) -0.6 -3.7, 2.4 0.675





    15-20 Kg 104 (33%) -0.7 -3.7, 2.4 0.669





Length at 3 years (cm) 312 0.0 -0.4, 0.3 0.902





Length at 3 years









    81-93 cm 95 (30%)






    94-95 cm 109 (35%) -1.0 -4.1, 2.1 0.532





    96-106 cm 108 (35%) 0.2 -2.9, 3.3 0.913





Child sex









    Male 167 (53%)


    Female 148 (47%) 0.5 -2.0, 2.9 0.708 0.1 -2.6, 2.9 0.934 0.2 -2.6, 2.9 0.907
Maternal education









    ≥5 years after graduation 182 (58%)






    3-4 years after graduation 86 (27%) 0.8 -2.0, 3.7 0.562





    2 years or less after graduation 45 (14%) 0.2 -3.5, 3.8 0.926





Maternal education









    ≥5 years after graduation 182 (58%)


    <5 years after graduation 131 (42%) 0.6 -1.9, 3.1 0.630 1.2 -1.4, 3.8 0.363 1.2 -1.4, 3.9 0.357
Maternal age at conception (years) 315 0.2 -0.2, 0.5 0.349 0.1 -0.3, 0.4 0.649 0.1 -0.3, 0.4 0.665
Maternal BMI before pregnancy (kg/m2) 314 -0.1 -0.4, 0.3 0.646





Maternal BMI before pregnancy









    <19 Kg/m2 45 (14%)


    19-23.9 Kg/m2 198 (63%) 0.9 -2.7, 4.5 0.622 0.5 -3.2, 4.3 0.772 0.6 -3.2, 4.3 0.764
    ≥24 Kg/m2 71 (23%) 1.7 -2.5, 5.9 0.429 1.6 -2.7, 6.0 0.464 1.6 -2.8, 5.9 0.483
Maternal parity









    None 139 (44%)


    1 child or more 176 (56%) 2.6 0.1, 5.0 0.041 2.4 -0.4, 5.2 0.089 2.3 -0.5, 5.1 0.104
Breastfeeding duration









    Not breastfed 25 (8.1%)


    <24 weeks 102 (33%) 3.6 -1.2, 8.4 0.138 3.3 -1.7, 8.3 0.200 3.2 -1.8, 8.2 0.210
    24-47 weeks 108 (35%) 5.3 0.5, 10.0 0.030 5.1 0.0, 10.1 0.048 5.0 0.0, 10.1 0.050
    Still breastfeed at 48 weeks 72 (23%) 6.1 1.1, 11.1 0.016 6.7 1.5, 11.9 0.011 6.7 1.4, 11.9 0.013
Gestational duration, completed weeks 315 0.0 -0.8, 0.8 0.948 0.0 -1.0, 1.0 0.982 0.0 -0.9, 1.0 0.928
Delivery mode









    Vaginal delivery 263 (83%)


    C-section 52 (17%) -2.3 -5.6, 1.1 0.182 -2.4 -6.0, 1.1 0.176 -2.4 -5.9, 1.2 0.190
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 232 (80%)


    Between 6 and 12 months old 45 (16%) -0.8 -4.4, 2.9 0.672 -0.4 -3.8, 3.1 0.840 -0.4 -3.9, 3.1 0.814
    Not introduced at 12 months old 13 (4.5%) -3.0 -9.3, 3.4 0.357 -2.2 -8.8, 4.3 0.501 -2.1 -8.6, 4.4 0.525
Presence of pets









    No 203 (73%)


    One or more 77 (28%) -1.4 -4.4, 1.5 0.339 -1.6 -4.7, 1.4 0.297 -1.6 -4.7, 1.5 0.312
Antibiotics use between 0-12 months old









    No 212 (68%)


    Yes 102 (32%) 1.6 -1.0, 4.2 0.225 1.7 -1.2, 4.5 0.248 1.7 -1.2, 4.5 0.250
Learning materials score at 3 years of age (HOME questionnaire) 309 0.7 -0.2, 1.6 0.117





Language stimulation score at 3 years of age (HOME questionnaire) 309 -0.2 -1.8, 1.4 0.799





Academic stimulation score at 3 years of age (HOME questionnaire) 309 0.0 -1.4, 1.4 0.989





Variety score at 3 years of age (HOME questionnaire) 309 0.5 -0.6, 1.7 0.358





HOME questionnaire total score 309 0.3 -0.2, 0.7 0.274 0.4 -0.2, 0.9 0.171 0.4 -0.2, 0.9 0.178
Maternal anxiety score during the third trimester of pregnancy 308 -0.4 -0.9, 0.0 0.048





Maternal depression score during the third trimester of pregnancy 307 0.3 -0.1, 0.8 0.167





Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.1 -0.3, 0.2 0.707 0.0 -0.3, 0.3 0.853 -0.1 -0.4, 0.3 0.751
Maternal anxiety score when child is one year old 254 -0.4 -0.8, 0.1 0.127





Maternal depression score when child is one year old 254 0.5 0.0, 1.0 0.068





Maternal anxiety and depression score when child is one year old 254 0.0 -0.3, 0.3 0.917





Maternal active smoking during pregnancy









    No 272 (93%)


    Yes 19 (6.5%) -2.0 -7.2, 3.2 0.453 -1.6 -7.0, 3.7 0.552 -1.6 -7.0, 3.7 0.551
Maternal passive smoking during pregnancy









    No 248 (82%)






    Yes 54 (18%) -1.5 -4.8, 1.8 0.370





Child passive smoking during the first year of life









    No 240 (76%)






    Yes 75 (24%) -1.2 -4.1, 1.7 0.431





Child perinatal exposure to tabacco up to one year









    No 198 (66%)






    Yes 103 (34%) -1.5 -4.2, 1.2 0.270





Child perinatal passive smoking up to one year









    No 205 (67%)


    Yes 100 (33%) -0.9 -3.6, 1.8 0.522 -0.6 -3.5, 2.3 0.678 -0.5 -3.4, 2.3 0.715
Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) -1.0 -3.9, 1.9 0.483





    Drank 67 (21%) -0.1 -3.6, 3.5 0.977





Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) -1.0 -3.9, 1.8 0.482





    <1drink/month when she knew she was pregnant 58 (19%) 0.8 -2.9, 4.4 0.682





    >1drink/month when she knew she was pregnant 9 (2.9%) -5.3 -12.9, 2.4 0.175





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 183 (61%)






    Other 116 (39%) 1.1 -1.6, 3.7 0.425





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 246 (82%)




    Other 53 (18%) -1.8 -5.2, 1.5 0.286 -3.4 -6.9, 0.1 0.058


Main mode of child care up to 1 year









    Collective day care 251 (84%)




    Other 48 (16%) -1.4 -4.9, 2.1 0.447


-2.7 -6.3, 1.0 0.148
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 53 (18%)






    Nursery assistant (out child home) 130 (43%) -0.7 -4.3, 3.0 0.714





    Other 116 (39%) 0.6 -3.1, 4.3 0.753





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 94 (31%)






    Nursery assistant (out child home) 152 (51%) -1.5 -4.4, 1.4 0.301





    Other 53 (18%) -2.8 -6.6, 1.0 0.153





Main mode of child care up to 1 year









    Collective day care 96 (32%)






    Nursery assistant (out child home) 155 (52%) -1.8 -4.6, 1.1 0.233





    Other 48 (16%) -2.4 -6.4, 1.5 0.223





Paternal education









    ≥5 years after graduation 142 (63%)






    3-4 years after graduation 39 (17%) -1.5 -5.5, 2.5 0.454





    2 years or less after graduation 43 (19%) -2.7 -6.5, 1.1 0.166





Paternal age at child birth (years) 283 0.1 -0.1, 0.4 0.343





Paternal age at child birth









    23-31 years 90 (32%)






    32-36 years 94 (33%) 0.4 -2.7, 3.6 0.782





    37-72 years 99 (35%) 0.9 -2.2, 4.0 0.576





Child age at the IQ 3 years evaluation 315 0.0 -0.3, 0.3 0.862





Child age at the IQ 3 years evaluation



0.0 -0.3, 0.3 0.939 0.0 -0.3, 0.3 0.940
No. Obs.



315

315





0.078

0.073

Adjusted R²









1 N; n (%)
2 CI = Confidence Interval
Figure 73: Multivariate model hypothesis checking (outcome is IQ visuospacial score Y3, before inclusion of microbiota variables)

IQ work memory score Y3

Table 17:

Influence of maternal and child characteristics on the IQ work memory score at 3 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 315 -1.6 -4.3, 1.2 0.258





Birth weight









    <3 Kg 63 (20%)


    3-3.4 Kg 159 (50%) 0.8 -2.4, 4.1 0.610 0.3 -3.6, 4.3 0.875 0.1 -3.9, 4.0 0.974
    ≥3.5 Kg 93 (30%) -1.4 -4.9, 2.1 0.441 -2.2 -7.2, 2.8 0.390 -2.4 -7.4, 2.7 0.354
Birth length (cm) 314 -0.1 -0.6, 0.5 0.785





Birth length









    <50 cm 116 (37%)


    50-51 cm 124 (39%) 0.0 -2.9, 2.8 0.973 0.3 -3.1, 3.7 0.846 0.4 -3.0, 3.8 0.822
    ≥52 cm 74 (24%) -1.3 -4.6, 1.9 0.415 0.0 -4.5, 4.5 0.998 0.1 -4.4, 4.6 0.959
Weight at one year (Kg) 312 -1.6 -2.8, -0.4 0.008





Weight at one year









    <8.5 Kg 56 (18%)






    8.5-9.9 Kg 174 (56%) -2.6 -5.9, 0.7 0.116





    ≥10 Kg 82 (26%) -5.0 -8.7, -1.3 0.009





Length at one year (cm) 306 -0.4 -0.8, 0.0 0.080





Length at one year









    <75 cm 116 (38%)






    75-77.9 cm 109 (36%) -2.8 -5.7, 0.1 0.055





    ≥78 cm 81 (26%) -2.8 -5.9, 0.3 0.078





Weight at 3 years (Kg) 314 -0.9 -1.6, -0.1 0.025





Weight at 3 years









    9-13 Kg 104 (33%)






    14 Kg 106 (34%) -0.9 -3.9, 2.1 0.563





    15-20 Kg 104 (33%) -2.5 -5.5, 0.5 0.098





Length at 3 years (cm) 312 -0.3 -0.6, 0.1 0.109





Length at 3 years









    81-93 cm 95 (30%)






    94-95 cm 109 (35%) -2.7 -5.7, 0.4 0.084





    96-106 cm 108 (35%) -2.0 -5.1, 1.0 0.193





Child sex









    Male 167 (53%)


    Female 148 (47%) 1.7 -0.7, 4.2 0.169 1.3 -1.4, 4.0 0.353 1.3 -1.4, 4.0 0.341
Maternal education









    ≥5 years after graduation 182 (58%)






    3-4 years after graduation 86 (27%) 0.5 -2.4, 3.3 0.746





    2 years or less after graduation 45 (14%) -0.8 -4.4, 2.8 0.674





Maternal education









    ≥5 years after graduation 182 (58%)


    <5 years after graduation 131 (42%) 0.0 -2.5, 2.5 0.974 0.2 -2.4, 2.8 0.886 0.2 -2.4, 2.8 0.884
Maternal age at conception (years) 315 -0.1 -0.5, 0.2 0.362 -0.2 -0.6, 0.1 0.239 -0.2 -0.6, 0.1 0.231
Maternal BMI before pregnancy (kg/m2) 314 0.0 -0.4, 0.3 0.870





Maternal BMI before pregnancy









    <19 Kg/m2 45 (14%)


    19-23.9 Kg/m2 198 (63%) -2.1 -5.7, 1.4 0.240 -3.0 -6.7, 0.7 0.111 -2.9 -6.6, 0.7 0.117
    ≥24 Kg/m2 71 (23%) -1.1 -5.2, 3.0 0.597 -1.6 -5.8, 2.7 0.477 -1.6 -5.9, 2.7 0.464
Maternal parity









    None 139 (44%)


    1 child or more 176 (56%) 1.7 -0.7, 4.2 0.167 2.9 0.2, 5.7 0.036 2.8 0.1, 5.6 0.044
Breastfeeding duration









    Not breastfed 25 (8.1%)


    <24 weeks 102 (33%) 0.7 -4.1, 5.5 0.779 0.8 -4.3, 5.8 0.767 0.7 -4.3, 5.7 0.782
    24-47 weeks 108 (35%) 0.1 -4.7, 4.9 0.970 -0.6 -5.6, 4.3 0.804 -0.7 -5.6, 4.3 0.796
    Still breastfeed at 48 weeks 72 (23%) 4.0 -1.0, 9.0 0.117 4.2 -1.0, 9.3 0.112 4.1 -1.1, 9.2 0.120
Gestational duration, completed weeks 315 0.0 -0.8, 0.8 0.970 0.2 -0.8, 1.1 0.731 0.2 -0.8, 1.2 0.681
Delivery mode









    Vaginal delivery 263 (83%)


    C-section 52 (17%) -1.3 -4.6, 2.0 0.447 -0.5 -3.9, 3.0 0.795 -0.4 -3.9, 3.1 0.828
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 232 (80%)


    Between 6 and 12 months old 45 (16%) -1.7 -5.2, 1.8 0.349 -0.5 -4.0, 3.0 0.775 -0.6 -4.1, 3.0 0.754
    Not introduced at 12 months old 13 (4.5%) -4.2 -10.3, 1.9 0.176 -3.7 -10.3, 2.9 0.269 -3.6 -10.3, 3.0 0.281
Presence of pets









    No 203 (73%)


    One or more 77 (28%) -0.8 -3.7, 2.1 0.600 -0.7 -3.8, 2.3 0.636 -0.7 -3.8, 2.4 0.643
Antibiotics use between 0-12 months old









    No 212 (68%)


    Yes 102 (32%) 0.9 -1.7, 3.5 0.506 1.0 -1.8, 3.8 0.469 1.0 -1.8, 3.8 0.467
Learning materials score at 3 years of age (HOME questionnaire) 309 0.3 -0.7, 1.2 0.580





Language stimulation score at 3 years of age (HOME questionnaire) 309 1.4 -0.1, 3.0 0.071





Academic stimulation score at 3 years of age (HOME questionnaire) 309 0.8 -0.6, 2.2 0.248





Variety score at 3 years of age (HOME questionnaire) 309 -0.3 -1.4, 0.8 0.591





HOME questionnaire total score 309 0.2 -0.2, 0.7 0.328 0.3 -0.2, 0.8 0.220 0.3 -0.2, 0.8 0.228
Maternal anxiety score during the third trimester of pregnancy 308 -0.3 -0.7, 0.1 0.158





Maternal depression score during the third trimester of pregnancy 307 -0.1 -0.6, 0.3 0.619





Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.1 -0.4, 0.1 0.279 -0.1 -0.4, 0.2 0.360 -0.1 -0.4, 0.1 0.303
Maternal anxiety score when child is one year old 254 -0.1 -0.5, 0.4 0.782





Maternal depression score when child is one year old 254 0.0 -0.5, 0.5 0.977





Maternal anxiety and depression score when child is one year old 254 0.0 -0.3, 0.3 0.850





Maternal active smoking during pregnancy









    No 272 (93%)


    Yes 19 (6.5%) -4.8 -9.9, 0.3 0.062 -3.8 -9.3, 1.6 0.166 -3.9 -9.3, 1.6 0.166
Maternal passive smoking during pregnancy









    No 248 (82%)






    Yes 54 (18%) -1.3 -4.6, 1.9 0.430





Child passive smoking during the first year of life









    No 240 (76%)






    Yes 75 (24%) -2.2 -5.0, 0.7 0.139





Child perinatal exposure to tabacco up to one year









    No 198 (66%)






    Yes 103 (34%) -1.5 -4.1, 1.1 0.254





Child perinatal passive smoking up to one year









    No 205 (67%)


    Yes 100 (33%) -1.0 -3.6, 1.7 0.468 0.2 -2.7, 3.1 0.910 0.2 -2.7, 3.1 0.881
Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) -0.4 -3.2, 2.5 0.800





    Drank 67 (21%) -0.9 -4.4, 2.6 0.613





Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) -0.4 -3.2, 2.5 0.800





    <1drink/month when she knew she was pregnant 58 (19%) -0.5 -4.2, 3.1 0.769





    >1drink/month when she knew she was pregnant 9 (2.9%) -3.1 -10.7, 4.5 0.416





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 183 (61%)






    Other 116 (39%) -0.6 -3.2, 1.9 0.634





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 246 (82%)




    Other 53 (18%) -1.6 -4.9, 1.6 0.326 -2.8 -6.3, 0.7 0.117


Main mode of child care up to 1 year









    Collective day care 251 (84%)




    Other 48 (16%) -1.0 -4.4, 2.4 0.563


-2.0 -5.8, 1.8 0.294
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 53 (18%)






    Nursery assistant (out child home) 130 (43%) -1.0 -4.5, 2.5 0.581





    Other 116 (39%) -1.3 -4.9, 2.3 0.468





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 94 (31%)






    Nursery assistant (out child home) 152 (51%) -1.3 -4.1, 1.6 0.383





    Other 53 (18%) -2.4 -6.1, 1.3 0.202





Main mode of child care up to 1 year









    Collective day care 96 (32%)






    Nursery assistant (out child home) 155 (52%) -1.4 -4.2, 1.4 0.314





    Other 48 (16%) -1.9 -5.7, 1.9 0.331





Paternal education









    ≥5 years after graduation 142 (63%)






    3-4 years after graduation 39 (17%) -0.8 -4.7, 3.1 0.678





    2 years or less after graduation 43 (19%) 1.0 -2.7, 4.7 0.599





Paternal age at child birth (years) 283 0.1 -0.2, 0.3 0.532





Paternal age at child birth









    23-31 years 90 (32%)






    32-36 years 94 (33%) 1.2 -1.9, 4.4 0.439





    37-72 years 99 (35%) 0.7 -2.4, 3.9 0.641





Child age at the IQ 3 years evaluation 315 0.1 -0.2, 0.4 0.493





Child age at the IQ 3 years evaluation



0.1 -0.2, 0.4 0.665 0.1 -0.2, 0.4 0.663
No. Obs.



315

315





0.088

0.085

Adjusted R²



0.008




1 N; n (%)
2 CI = Confidence Interval
Figure 74: Multivariate model hypothesis checking (outcome is IQ work memory score Y3, before inclusion of microbiota variables)

IQ total score Y3

Table 18:

Influence of maternal and child characteristics on the IQ total score at 3 years (uni and multivariate models).

Characteristic Univariate models Multivariate model test 1 Multivariate model test 2
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight (Kg) 315 -1.0 -3.8, 1.8 0.490





Birth weight









    <3 Kg 63 (20%)


    3-3.4 Kg 159 (50%) 0.5 -2.8, 3.8 0.781 1.2 -2.8, 5.2 0.552 0.9 -3.1, 4.9 0.675
    ≥3.5 Kg 93 (30%) -0.3 -4.0, 3.3 0.854 0.3 -4.8, 5.5 0.896 0.1 -5.0, 5.2 0.970
Birth length (cm) 314 0.0 -0.6, 0.6 0.968





Birth length









    <50 cm 116 (37%)


    50-51 cm 124 (39%) -0.3 -3.1, 2.6 0.858 -0.2 -3.7, 3.2 0.888 -0.2 -3.6, 3.3 0.928
    ≥52 cm 74 (24%) -0.6 -3.9, 2.7 0.731 0.4 -4.2, 5.0 0.861 0.6 -4.1, 5.2 0.803
Weight at one year (Kg) 312 -0.8 -2.1, 0.4 0.188





Weight at one year









    <8.5 Kg 56 (18%)






    8.5-9.9 Kg 174 (56%) -1.6 -5.0, 1.8 0.358





    ≥10 Kg 82 (26%) -2.6 -6.5, 1.2 0.182





Length at one year (cm) 306 -0.3 -0.8, 0.1 0.141





Length at one year









    <75 cm 116 (38%)






    75-77.9 cm 109 (36%) -3.6 -6.6, -0.7 0.016





    ≥78 cm 81 (26%) -2.6 -5.8, 0.6 0.107





Weight at 3 years (Kg) 314 -0.1 -0.9, 0.6 0.716





Weight at 3 years









    9-13 Kg 104 (33%)






    14 Kg 106 (34%) -1.6 -4.6, 1.5 0.320





    15-20 Kg 104 (33%) -1.1 -4.2, 2.0 0.485





Length at 3 years (cm) 312 -0.1 -0.4, 0.3 0.729





Length at 3 years









    81-93 cm 95 (30%)






    94-95 cm 109 (35%) -1.6 -4.7, 1.6 0.324





    96-106 cm 108 (35%) -0.1 -3.2, 3.1 0.963





Child sex









    Male 167 (53%)


    Female 148 (47%) 2.1 -0.4, 4.6 0.099 1.4 -1.4, 4.1 0.319 1.5 -1.3, 4.2 0.301
Maternal education









    ≥5 years after graduation 182 (58%)






    3-4 years after graduation 86 (27%) 0.7 -2.2, 3.6 0.643





    2 years or less after graduation 45 (14%) -1.5 -5.3, 2.2 0.412





Maternal education









    ≥5 years after graduation 182 (58%)


    <5 years after graduation 131 (42%) -0.1 -2.6, 2.5 0.951 0.7 -2.0, 3.3 0.606 0.7 -1.9, 3.4 0.600
Maternal age at conception (years) 315 0.0 -0.3, 0.4 0.805 0.0 -0.3, 0.4 0.829 0.0 -0.3, 0.4 0.852
Maternal BMI before pregnancy (kg/m2) 314 0.0 -0.4, 0.3 0.828





Maternal BMI before pregnancy









    <19 Kg/m2 45 (14%)


    19-23.9 Kg/m2 198 (63%) 0.5 -3.1, 4.2 0.779 0.0 -3.7, 3.8 0.991 0.1 -3.7, 3.8 0.975
    ≥24 Kg/m2 71 (23%) 1.3 -3.0, 5.5 0.560 1.0 -3.3, 5.4 0.643 0.9 -3.4, 5.3 0.670
Maternal parity









    None 139 (44%)


    1 child or more 176 (56%) 0.3 -2.2, 2.8 0.799 0.8 -2.0, 3.6 0.583 0.6 -2.2, 3.4 0.657
Breastfeeding duration









    Not breastfed 25 (8.1%)


    <24 weeks 102 (33%) 2.3 -2.6, 7.3 0.358 1.6 -3.4, 6.7 0.526 1.6 -3.5, 6.7 0.545
    24-47 weeks 108 (35%) 3.8 -1.1, 8.7 0.129 3.0 -2.0, 8.1 0.235 3.0 -2.0, 8.0 0.243
    Still breastfeed at 48 weeks 72 (23%) 5.9 0.7, 11.0 0.026 6.3 1.1, 11.6 0.018 6.2 1.0, 11.5 0.021
Gestational duration, completed weeks 315 -0.2 -1.0, 0.7 0.703 -0.2 -1.2, 0.8 0.661 -0.2 -1.2, 0.8 0.730
Delivery mode









    Vaginal delivery 263 (83%)


    C-section 52 (17%) -1.6 -5.0, 1.7 0.343 -1.8 -5.3, 1.7 0.316 -1.7 -5.3, 1.9 0.345
Period of introduction of solid food 0-12 months old









    Between 0 and 6 months old 232 (80%)


    Between 6 and 12 months old 45 (16%) -0.4 -4.0, 3.2 0.845 0.3 -3.3, 4.0 0.861 0.3 -3.4, 4.0 0.893
    Not introduced at 12 months old 13 (4.5%) -6.9 -13.2, -0.6 0.031 -5.4 -12.2, 1.4 0.120 -5.2 -12.1, 1.6 0.130
Presence of pets









    No 203 (73%)


    One or more 77 (28%) -0.9 -3.8, 2.1 0.566 -0.8 -4.0, 2.3 0.597 -0.8 -4.0, 2.4 0.614
Antibiotics use between 0-12 months old









    No 212 (68%)


    Yes 102 (32%) 0.5 -2.1, 3.2 0.691 0.7 -2.1, 3.5 0.637 0.7 -2.1, 3.5 0.638
Learning materials score at 3 years of age (HOME questionnaire) 309 1.5 0.5, 2.4 0.002





Language stimulation score at 3 years of age (HOME questionnaire) 309 0.8 -0.8, 2.3 0.337





Academic stimulation score at 3 years of age (HOME questionnaire) 309 1.3 -0.1, 2.7 0.077





Variety score at 3 years of age (HOME questionnaire) 309 0.3 -0.9, 1.4 0.650





HOME questionnaire total score 309 0.6 0.2, 1.1 0.009 0.6 0.1, 1.1 0.017 0.6 0.1, 1.1 0.019
Maternal anxiety score during the third trimester of pregnancy 308 -0.5 -1.0, -0.1 0.015





Maternal depression score during the third trimester of pregnancy 307 0.1 -0.4, 0.5 0.828





Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.2 -0.5, 0.1 0.187 -0.1 -0.5, 0.2 0.364 -0.2 -0.5, 0.1 0.280
Maternal anxiety score when child is one year old 254 -0.4 -0.9, 0.0 0.076





Maternal depression score when child is one year old 254 0.1 -0.4, 0.6 0.607





Maternal anxiety and depression score when child is one year old 254 -0.1 -0.4, 0.2 0.419





Maternal active smoking during pregnancy









    No 272 (93%)


    Yes 19 (6.5%) -3.0 -8.3, 2.2 0.257 -1.8 -7.2, 3.6 0.522 -1.8 -7.2, 3.6 0.522
Maternal passive smoking during pregnancy









    No 248 (82%)






    Yes 54 (18%) -2.1 -5.4, 1.2 0.220





Child passive smoking during the first year of life









    No 240 (76%)






    Yes 75 (24%) -2.0 -5.0, 0.9 0.175





Child perinatal exposure to tabacco up to one year









    No 198 (66%)






    Yes 103 (34%) -1.9 -4.6, 0.8 0.158





Child perinatal passive smoking up to one year









    No 205 (67%)


    Yes 100 (33%) -1.3 -4.0, 1.5 0.362 -0.5 -3.4, 2.4 0.731 -0.4 -3.3, 2.5 0.774
Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) 0.6 -2.3, 3.5 0.697





    Drank 67 (21%) -0.8 -4.4, 2.7 0.641





Maternal alcohol consumption during pregnancy









    Did not drink 95 (30%)






    Drank only before finding out she was pregnant 151 (48%) 0.6 -2.3, 3.5 0.696





    <1drink/month when she knew she was pregnant 58 (19%) 0.2 -3.5, 3.9 0.933





    >1drink/month when she knew she was pregnant 9 (2.9%) -7.3 -15.1, 0.4 0.064





Main mode of child care at 6 months (2 categories, optimized 2)









    Collective day care 183 (61%)






    Other 116 (39%) -0.1 -2.7, 2.6 0.954





Main mode of child care at 12 months (2 categories, optimized 2)









    Collective day care 246 (82%)




    Other 53 (18%) -3.1 -6.5, 0.2 0.068 -4.2 -7.8, -0.7 0.020


Main mode of child care up to 1 year









    Collective day care 251 (84%)




    Other 48 (16%) -2.5 -6.0, 1.0 0.165


-3.2 -6.9, 0.5 0.086
Main mode of child care at 6 months (3 categories, optimized 2)









    Collective day care 53 (18%)






    Nursery assistant (out child home) 130 (43%) 0.3 -3.3, 3.9 0.878





    Other 116 (39%) 0.1 -3.6, 3.8 0.947





Main mode of child care at 12 months (3 categories, optimized 2)









    Collective day care 94 (31%)






    Nursery assistant (out child home) 152 (51%) -1.5 -4.4, 1.4 0.300





    Other 53 (18%) -4.1 -7.9, -0.3 0.036





Main mode of child care up to 1 year









    Collective day care 96 (32%)






    Nursery assistant (out child home) 155 (52%) -1.7 -4.6, 1.1 0.236





    Other 48 (16%) -3.5 -7.5, 0.4 0.076





Paternal education









    ≥5 years after graduation 142 (63%)






    3-4 years after graduation 39 (17%) -0.3 -4.4, 3.8 0.883





    2 years or less after graduation 43 (19%) -2.6 -6.5, 1.4 0.202





Paternal age at child birth (years) 283 0.1 -0.2, 0.3 0.509





Paternal age at child birth









    23-31 years 90 (32%)






    32-36 years 94 (33%) 1.2 -2.0, 4.3 0.475





    37-72 years 99 (35%) 0.0 -3.2, 3.1 0.995





Child age at the IQ 3 years evaluation 315 0.1 -0.1, 0.4 0.323





Child age at the IQ 3 years evaluation



0.1 -0.2, 0.4 0.499 0.1 -0.2, 0.4 0.499
No. Obs.



315

315





0.099

0.091

Adjusted R²



0.020

0.011

1 N; n (%)
2 CI = Confidence Interval
Figure 75: Multivariate model hypothesis checking (outcome is IQ total score Y3, before inclusion of microbiota variables)

Part 3: Main analysis

Final covariates

Justification du choix des covariables inclues dans le modèle et leur codage :

  • Age de l’enfant lors du test de neurodeveloppement :

    • Distribution : ok (Table 6, Figure 37, Figure 38, Figure 39)

    • Données manquantes : CBCL (20/356 (5.6%)), IQ (41/356 (12%)), SRS et BRIEF-P (15/356 (4.2%)) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) : non statistiquement associé avec les outcomes neurodeveloppement sauf un tendance (p<0.1) pour l’IQ verbal comprenhension Table 15)

      --> Choix final : les variables sont inclues, selon l’outcome, en continue

  • Poids et taille de l’enfant à la naissance, à un an ou 3 ans :

    • Distribution : ok (Table 6, Figure 57, Figure 58, Figure 59, Figure 60, Figure 61, Figure 62)

    • Corrélations : les variables sont corrélées (Figure 36)

    • Données manquantes : le poids et la taille à la naissance sont les variables avec le moins de données manquantes (<2% VS autour de 15-20% pour les autres, Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • Les relations ne semblent pas linéaires entre le poids et la taille à la naissance et le neurodéveloppement de l’enfant (Table 7 à Table 18)
    • Elimination du poids et de la taille à 1, 2 et 3 ans pour respecter la chronologie (le microbiote a été prélevé à un an)

      --> Choix final: on choisit les variables poids et taille à la naissance, en catégoriel (3 catégories, po_w_kg_3cat et po_he_3cat)

  • Age des parents :

    • Distribution : ok (Table 6, Figure 40, Figure 41)

    • Corrélations : les variables âge de la mère à la conception et âge du père à la naissance sont corrélées (Figure 36)

    • Données manquantes : l’âge de la mère n’a aucune donnée manquante contrairement à l’âge du père (17% de NA, Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • l’âge du père et de la mère sont associés au comportement de l’enfant mais pas au qi les deux variables semblent avoir une relation linéaire les deux variables sont associées dans le même sens

      --> Choix final : on choisit la variable âge de la mère, en continu (mo_age)

  • Niveau d’éducation des parents:

    • Distribution : ok, catégories équilibrées (Table 5)

    • Données manquantes : il y a moins de données manquantes sur la variables mère (0.4% VS 39%, Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • le niveau d’éducation de la mère est associée à SRS totale et Plan/organization score at 3 years (BRIEF-P) à trois ans
    • Choix des catégories : Ariane et Vicente ont utilisé 2 catégories (≥5 years after graduation VS <5 years after graduation)

      --> Choix final : on choisit la variable éducation de la mère en 2 catégories (mo_dipl_2cat)

  • IMC de la mère avant la grossesse :

    • Distribution : beaucoup d’outliers (Table 6, Figure 42)

    • Données manquantes : 1/356 (0.3%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • L’IMC de la mère avant la grossesse n’est pas statistiquement associée aux outcomes de neurodeveloppement

      • La relation ne semble pas linéaire

Choix final : on choisit la variable IMC de la mère avant la grossesse en 3 catégories (mo_bmi_bepr_3cat)

  • Sexe de l’enfant :

    • Distribution (Male/Female): ok, catégories équilibrées (Table 5)

    • Données manquantes : 0/356 (0%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • Le sexe de l’enfant n’est pas associé aux outcomes de neurodeveloppement

      • Sauf en univarié pour BRIEF-P inhibit score (Beta : -1.2; CI95%:-2.3, 0.0; p=0.042, female compared to male, Table 10)

      • Sauf en univarié pour IQ verbal comprehension score Y3 (Beta : 2.6; CI95% : 0.0, 5.1; p=0.046, female, compared to male, Table 15)

Choix final : on inclut la variable sexe de l’enfant (ch_sex)

  • Parité :

    • Distribution (None/1 child or more) : ok, catégories équilibrées (Table 5)

    • Données manquantes : 0/356 (0%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • Statistiquement associé avec presque tous les outcomes de neurodeveloppement

      • Le fait d’avoir déjà eu un enfant ou plus est associé à une diminution des outcomes BRIEF-P, SRS, CBCL et une augmentation du QI

      • Sauf IQ verbal comprehension score Y3 : sens de l’association innatendu

Choix final : on inclut la variable parité (mo_par_2cat)

  • Durée de l’allaitement :

    • Distribution : ok, pas d’outliers (Figure 49, Table 6)

    • Données manquantes : 9/356 (2.5%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • La relation entre la durée de l’allaitement et les outcomes de neuroveloppement semble linéaire

Choix final : on inclut la variable catégorielle car pour le microbiote il y a une grosse différenc eattendu entre les enfants allaités des enfants non allaités (ch_bf_duration_till48w_4cat)

  • Durée de la gestation :

    • Distribution : ok (Figure 50, Table 6)

    • Données manquantes : 0/356 (0%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • La durée de la gestation n’est pas statistiquement associée aux outcomes de neurodeveloppement (car les enfants sont presque tous nés à terme)

Choix final : on inclut la variable en continue (po_gd)

  • Mode d’accouchement :

    • Distribution (Vaginal delivery / C-section) : ok (Table 5)

    • Données manquantes : 0/356 (0%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • Le mode d’accouchement n’est pas statistiquement associé aux outcomes de neurodeveloppement

Choix final : on inclut la variable en continue (po_delmod)

  • Période d’introduction de la nourriture solide :

    • Distribution (Between 0 and 6 months old / Between 6 and 12 months old / Not introduced at 12 months old) : ok (Table 5)

    • Données manquantes : 37/356 (10%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18)

Choix final : on inclut la variable en catégoriel (ch_food_intro_Y1_3cat)

  • Présence d’animaux de compagnie :

    • Distribution (No / One or more) : ok (Table 5)

    • Données manquantes : 45/356 (13%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • non statistiquement associé

Choix final : on inclut la variable en catégoriel (mo_pets)

  • Prescription d’antibiotiques entre la naissance et l’âge de 1 an :

    • Distribution (No / Yes) : ok (Table 5)

      • Données manquantes : 1/356 (0.3%) (Table 5)

      • Régressions uni et multivariées (Table 7 à Table 18) :

        • non statistiquement associé

Choix final : on inclut la variable en catégoriel (ch_antibio_Y1_2cat)

  • Questionnaires HOME à 3 ans :

    • Corrélations : les variables HOME sont corrélées entre elles (Figure 36) –> on choisit la plus générale (home_total_y3)

    • Distribution : continue, ok (Table 6, Figure 52, Figure 53, Figure 54, Figure 56)

    • Données manquantes : 43/356 (12%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • HOME questionnaire total score était associé à CBCL externe score Y2, SRS total score Y3, IQ verbal comprehension score Y3, IQ total score Y3

Choix final : on inclut la variable en continue (home_total_y3)

  • Score d’anxiété et de dépression de la mère, au 3ème trimestre et lorsque l’enfant a l’âge de 1 ans :

    • Corrélations : les variables sont corrélées entre elles (Figure 36) –> on choisit la plus générale et la plus loin chronologiquement des variables d’expositions et d’outcomes –> le score totale d’anxiété et de dépression de la mère au T3

    • Distribution : continue, ok (Table 6, Figure 43, Figure 44, Figure 45, Figure 46, Figure 47, Figure 48) - Données manquantes : 14/356 (3.9%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • La variable score d’anxiété et de dépression de la mère à T3 est statistiquement associée aux outcomes de neurodeveloppmement (CBCL Y2, SRS Y3, BRIEF-P Y3) mais pas au QI

Choix final : on inclut la variable score totale d’anxiété et de dépression de la mère au T3 (mo_hadtotscore_grt3_imp)

  • Consomation d’alcool pendant la grossesse :

    • la variable est peu précise, peu de femme ont réélement bu pendant la grossesse (Table 5, Table 6)

Choix final : nous n’incluons pas cette variable dans les modèles

  • Tabagisme périnatale :

    • 3 variables initiales sont disponibles :

      • Tabagisme passif de la mère pendant la grossesse (oui/non)

      • Tabagisme actif de la mère pendant la grossesse (oui/non)

      • Tabagisme passif de l’enfant de la naissance à un an (oui/non)

    • Distribution (No / Yes) : ok (Table 5)

    • Données manquantes : ok (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • non statistiquement associé ou tendance (en univarié)

Choix final : on regroupe en 2 variables catégorielles oui / non

une variable tabagisme périnatale passif (tabagisme passif de la mère pendant la grossesse + tabagisme passif de l’enfant de la naissance à un an (ch_tabacco_passive_up_to_Y1)

une variable tabagisme actif de la mère pendant la grossesse (mo_tob_gr_anyt_yn_n2)

  • Mode de garde principal de l’enfant à 6 et 12 mois :

    • 2 variables sont disponibles : mode de garde à 6 mois (Collective day care/other), mode de garde à 12 mois (Collective day care/other)

    • on teste 2 models :

      • un premier où l’on inclut la variable main child care at 12 months (ch_care_main_12m_opt2_2c, Multivariate model test 1)

      • un deuxième où l’on inclut une variable main child care up to 12 months (ch_care_main_6m_12m_opt2_2c, Multivariate model test 2) : ici tous les enfants qui ont un mode de garde principal collectif à 6 ou 12 mois sont dans la catégorie collective day care

    • Distribution : ok, il n’y a pas une grande différence entre les deux variables (Table 5)

    • Données manquantes : 25/356 (7.0%) (Table 5)

    • Régressions uni et multivariées (Table 7 à Table 18) :

      • La variable main mode of child care at 12 months est associée à une augmentation de BRIEF-P shift score Y3 et à une diminition de IQ total scoreY3 (Collective day care est la catégorie de référence) dans les modèles uni et multivariés

      • La variable main mode of child care up to 12 months tendait à être associée à une augmentation de BRIEF-P shift score Y3 et à une diminition de IQ total scoreY3 (Collective day care est la catégorie de référence) dans les modèles uni et multivariés

Choix final : on inclut la variable en catégoriel (ch_care_main_12m_opt2_2c)

Table 19:

Description final covariates

Characteristic Included, N = 3561 Excluded, N = 1281 p-value2
Birth weight

0.96
    <3 Kg 74 (21%) 25 (20%)
    3-3.4 Kg 174 (49%) 62 (50%)
    ≥3.5 Kg 108 (30%) 36 (29%)
Birth length

0.44
    <50 cm 130 (37%) 40 (34%)
    50-51 cm 141 (40%) 54 (46%)
    ≥52 cm 84 (24%) 23 (20%)
Maternal education

0.80
    ≥5 years after graduation 201 (57%) 71 (55%)
    <5 years after graduation 153 (43%) 57 (45%)
Maternal age at conception (years) 32 (30, 35) 32 (30, 35) 0.29
Maternal BMI before pregnancy

0.40
    <19 Kg/m2 48 (14%) 12 (10%)
    19-23.9 Kg/m2 223 (63%) 78 (62%)
    ≥24 Kg/m2 84 (24%) 35 (28%)
Child sex

0.96
    Male 190 (53%) 66 (54%)
    Female 166 (47%) 57 (46%)
Maternal parity

0.88
    None 164 (46%) 58 (45%)
    1 child or more 192 (54%) 70 (55%)
Breastfeeding duration

0.54
    Not breastfed 29 (8%) 11 (12%)
    <24 weeks 122 (35%) 35 (37%)
    24-47 weeks 117 (34%) 32 (34%)
    Still breastfeed at 48 weeks 79 (23%) 16 (17%)
Gestational duration, completed weeks 40 (39, 40) 39 (38, 40) 0.31
Delivery mode

0.54
    Vaginal delivery 298 (84%) 100 (81%)
    C-section 58 (16%) 23 (19%)
Period of introduction of solid food 0-12 months old

0.09
    Between 0 and 6 months old 253 (79%) 40 (67%)
    Between 6 and 12 months old 50 (16%) 16 (27%)
    Not introduced at 12 months old 16 (5%) 4 (7%)
Presence of pets

0.30
    No 222 (71%) 49 (65%)
    One or more 89 (29%) 26 (35%)
Antibiotics use between 0-12 months old

0.02
    No 246 (69%) 86 (81%)
    Yes 109 (31%) 20 (19%)
HOME questionnaire total score 25 (23, 26) 25 (23, 27) 0.68
Maternal anxiety and depression score during the third trimester of pregnancy 10 (7, 13) 11 (7, 15) 0.16
Maternal active smoking during pregnancy

0.30
    No 310 (94%) 91 (91%)
    Yes 20 (6%) 9 (9%)
Child perinatal passive smoking up to one year

0.08
    No 232 (67%) 45 (57%)
    Yes 112 (33%) 34 (43%)
Main mode of child care at 12 months

0.28
    Collective day care 271 (82%) 55 (76%)
    Other 60 (18%) 17 (24%)
1 n (%); Median (IQR)
2 Pearson’s Chi-squared test; Wilcoxon rank sum test; Fisher’s exact test

Final sample sizes

Figure 76: Flow chart of the participants

A rediscuter si on prend un seul effectif commun ?

CBCL scores Y2

Interne score Y2

Table 20:

Adjusted associations between gut microbiota parameters and the CBCL interne score.

Characteristic Child CBCL interne score at 2 years
N Beta 95% CI1 p-value
Specific richness 332 0.01 -0.01, 0.03 0.536
Shannon diversity 332 0.38 -0.56, 1.33 0.424
Phylum Firmicutes 336 0.00 -0.03, 0.02 0.842
Phylum Actinobacteria 336 0.02 -0.01, 0.04 0.151
Phylum Bacteroidetes 336 0.00 -0.03, 0.03 0.869
Phylum Proteobacteria 336 -0.03 -0.06, 0.00 0.080
Genus Bifidobacterium 336 0.02 -0.01, 0.04 0.134
Genus Bacteroides 336 -0.02 -0.05, 0.02 0.323
Genus Blautia 336 -0.04 -0.09, 0.01 0.131
Genera Escherichia and Shigella 336 -0.02 -0.06, 0.01 0.210
1 CI = Confidence Interval

Externe score Y2

Table 21:

Adjusted associations between gut microbiota parameters and the CBCL externe score at 2 years.

Characteristic Child CBCL externe score at 2 years
N Beta 95% CI1 p-value
Specific richness 331 -0.01 -0.03, 0.02 0.629
Shannon diversity 331 0.50 -0.76, 1.75 0.436
Phylum Firmicutes 335 0.02 -0.01, 0.06 0.156
Phylum Actinobacteria 335 0.02 -0.01, 0.05 0.232
Phylum Bacteroidetes 335 -0.01 -0.05, 0.03 0.547
Phylum Proteobacteria 335 -0.05 -0.10, -0.01 0.024
Genus Bifidobacterium 335 0.02 -0.01, 0.05 0.203
Genus Bacteroides 335 -0.02 -0.06, 0.02 0.396
Genus Blautia 335 0.03 -0.04, 0.10 0.377
Genera Escherichia and Shigella 335 -0.04 -0.09, 0.01 0.158
1 CI = Confidence Interval

SRS total score Y3

Table 22:

Adjusted associations between gut microbiota parameters and the SRS total score at 3 years.

Characteristic Child SRS total score at 3 years
N Beta 95% CI1 p-value
Specific richness 327 0.02 -0.04, 0.07 0.570
Shannon diversity 327 -0.10 -2.58, 2.38 0.938
Phylum Firmicutes 332 -0.01 -0.08, 0.06 0.768
Phylum Actinobacteria 332 0.04 -0.02, 0.10 0.202
Phylum Bacteroidetes 332 0.02 -0.06, 0.10 0.647
Phylum Proteobacteria 332 -0.10 -0.19, -0.02 0.018
Genus Bifidobacterium 332 0.04 -0.02, 0.11 0.165
Genus Bacteroides 332 0.02 -0.06, 0.10 0.601
Genus Blautia 332 -0.05 -0.19, 0.09 0.511
Genera Escherichia and Shigella 332 -0.10 -0.20, -0.01 0.038
1 CI = Confidence Interval

BRIEF-P Y3

Inhibition score Y3

Table 23:

Adjusted associations between gut microbiota parameters and the BRIEF-P inhibition score at 3 years.

Characteristic Child inhibition score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness 325 0.00 -0.02, 0.03 0.711
Shannon diversity 325 0.07 -0.97, 1.11 0.894
Phylum Firmicutes 330 0.01 -0.01, 0.04 0.317
Phylum Actinobacteria 330 0.02 0.00, 0.05 0.099
Phylum Bacteroidetes 330 -0.02 -0.05, 0.02 0.358
Phylum Proteobacteria 330 -0.04 -0.07, 0.00 0.031
Genus Bifidobacterium 330 0.02 0.00, 0.05 0.103
Genus Bacteroides 330 -0.01 -0.05, 0.02 0.486
Genus Blautia 330 0.02 -0.04, 0.08 0.551
Genera Escherichia and Shigella 330 -0.02 -0.06, 0.02 0.291
1 CI = Confidence Interval

Shift score Y3

Table 24:

Adjusted associations between gut microbiota parameters and the BRIEF-P shift score at 3 years.

Characteristic Child shift score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness 333 0.00 -0.01, 0.01 0.766
Shannon diversity 333 -0.16 -0.75, 0.42 0.587
Phylum Firmicutes 338 0.00 -0.02, 0.02 0.992
Phylum Actinobacteria 338 0.01 -0.01, 0.02 0.352
Phylum Bacteroidetes 338 0.00 -0.02, 0.02 0.912
Phylum Proteobacteria 338 -0.02 -0.04, 0.00 0.126
Genus Bifidobacterium 338 0.01 -0.01, 0.02 0.280
Genus Bacteroides 338 0.00 -0.02, 0.02 0.653
Genus Blautia 338 -0.01 -0.05, 0.02 0.465
Genera Escherichia and Shigella 338 -0.01 -0.04, 0.01 0.238
1 CI = Confidence Interval

Emotional control score Y3

Table 25:

Adjusted associations between gut microbiota parameters and the BRIEF-P emotional control score at 3 years.

Characteristic Child emotional control score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness 332 0.01 0.00, 0.03 0.090
Shannon diversity 332 0.53 -0.16, 1.22 0.130
Phylum Firmicutes 337 0.01 -0.01, 0.03 0.500
Phylum Actinobacteria 337 0.00 -0.01, 0.02 0.735
Phylum Bacteroidetes 337 0.01 -0.01, 0.03 0.283
Phylum Proteobacteria 337 -0.03 -0.05, -0.01 0.017
Genus Bifidobacterium 337 0.00 -0.01, 0.02 0.715
Genus Bacteroides 337 0.02 -0.01, 0.04 0.185
Genus Blautia 337 0.00 -0.04, 0.04 0.888
Genera Escherichia and Shigella 337 -0.03 -0.06, 0.00 0.028
1 CI = Confidence Interval

Working memory score Y3

Table 26:

Adjusted associations between gut microbiota parameters and the BRIEF-P working memory score at 3 years.

Characteristic Child working memory score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness 324 0.01 -0.01, 0.03 0.430
Shannon diversity 324 0.05 -0.83, 0.92 0.915
Phylum Firmicutes 329 0.01 -0.01, 0.03 0.429
Phylum Actinobacteria 329 0.02 -0.01, 0.04 0.131
Phylum Bacteroidetes 329 -0.03 -0.06, 0.00 0.032
Phylum Proteobacteria 329 -0.02 -0.05, 0.01 0.125
Genus Bifidobacterium 329 0.02 0.00, 0.04 0.123
Genus Bacteroides 329 -0.03 -0.06, 0.00 0.031
Genus Blautia 329 -0.02 -0.07, 0.03 0.457
Genera Escherichia and Shigella 329 -0.03 -0.06, 0.01 0.126
1 CI = Confidence Interval

Plan/organization score Y3

Table 27:

Adjusted associations between gut microbiota parameters and the BRIEF-P plan and organization score at 3 years.

Characteristic Child plan/organization score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness 330 0.01 0.00, 0.02 0.149
Shannon diversity 330 0.19 -0.37, 0.74 0.508
Phylum Firmicutes 335 0.02 0.00, 0.03 0.026
Phylum Actinobacteria 335 0.01 -0.01, 0.02 0.417
Phylum Bacteroidetes 335 -0.02 -0.03, 0.00 0.045
Phylum Proteobacteria 335 -0.02 -0.03, 0.00 0.113
Genus Bifidobacterium 335 0.01 -0.01, 0.02 0.383
Genus Bacteroides 335 -0.02 -0.04, 0.00 0.032
Genus Blautia 335 0.00 -0.03, 0.03 >0.999
Genera Escherichia and Shigella 335 -0.01 -0.03, 0.01 0.246
1 CI = Confidence Interval

IQ Y3

Verbal comprehension score Y3

Table 28:

Adjusted associations between gut microbiota parameters and the IQ verbal comprehension score at 3 years.

Characteristic Child verbal comprehension score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness 310 -0.01 -0.06, 0.04 0.690
Shannon diversity 310 -1.28 -3.66, 1.10 0.290
Phylum Firmicutes 315 -0.02 -0.09, 0.04 0.535
Phylum Actinobacteria 315 -0.02 -0.08, 0.03 0.423
Phylum Bacteroidetes 315 0.03 -0.05, 0.10 0.473
Phylum Proteobacteria 315 0.00 -0.09, 0.08 0.960
Genus Bifidobacterium 315 -0.02 -0.08, 0.04 0.462
Genus Bacteroides 315 0.03 -0.04, 0.11 0.400
Genus Blautia 315 0.06 -0.08, 0.19 0.394
Genera Escherichia and Shigella 315 -0.05 -0.14, 0.05 0.361
1 CI = Confidence Interval

Visuospatiale score Y3

Table 29:

Adjusted associations between gut microbiota parameters and the IQ visuospatiale score at 3 years.

Characteristic Child visuospatiale score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness 310 0.00 -0.05, 0.05 0.922
Shannon diversity 310 0.35 -1.99, 2.69 0.768
Phylum Firmicutes 315 -0.01 -0.07, 0.06 0.781
Phylum Actinobacteria 315 0.00 -0.06, 0.06 0.908
Phylum Bacteroidetes 315 0.04 -0.03, 0.11 0.243
Phylum Proteobacteria 315 -0.03 -0.11, 0.05 0.500
Genus Bifidobacterium 315 0.00 -0.06, 0.06 0.911
Genus Bacteroides 315 0.05 -0.02, 0.13 0.174
Genus Blautia 315 0.00 -0.13, 0.13 0.985
Genera Escherichia and Shigella 315 -0.04 -0.14, 0.06 0.411
1 CI = Confidence Interval

Work memory score Y3

Table 30:

Adjusted associations between gut microbiota parameters and the IQ work memory score at 3 years.

Characteristic Child work memory score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness 310 -0.01 -0.05, 0.04 0.800
Shannon diversity 310 -1.04 -3.34, 1.25 0.372
Phylum Firmicutes 315 -0.01 -0.07, 0.06 0.819
Phylum Actinobacteria 315 0.03 -0.02, 0.09 0.261
Phylum Bacteroidetes 315 -0.02 -0.09, 0.06 0.669
Phylum Proteobacteria 315 -0.04 -0.12, 0.04 0.347
Genus Bifidobacterium 315 0.03 -0.03, 0.09 0.317
Genus Bacteroides 315 -0.01 -0.08, 0.07 0.814
Genus Blautia 315 0.00 -0.13, 0.13 0.956
Genera Escherichia and Shigella 315 -0.06 -0.16, 0.04 0.216
1 CI = Confidence Interval

Total IQ score Y3

Table 31:

Adjusted associations between gut microbiota parameters and the IQ total score at 3 years.

Characteristic Child total IQ score at 3 years
N Beta 95% CI1 p-value
Specific richness 310 0.00 -0.05, 0.05 0.997
Shannon diversity 310 -0.64 -3.00, 1.71 0.590
Phylum Firmicutes 315 -0.02 -0.09, 0.04 0.452
Phylum Actinobacteria 315 0.00 -0.06, 0.05 0.898
Phylum Bacteroidetes 315 0.04 -0.03, 0.11 0.310
Phylum Proteobacteria 315 -0.02 -0.11, 0.06 0.610
Genus Bifidobacterium 315 0.00 -0.06, 0.05 0.886
Genus Bacteroides 315 0.05 -0.03, 0.12 0.205
Genus Blautia 315 0.03 -0.10, 0.16 0.687
Genera Escherichia and Shigella 315 -0.06 -0.15, 0.04 0.249
1 CI = Confidence Interval

Part 4: Additional analysis

Covariates effects on the outcomes

CBCL Y2

Interne score Y2

Characteristic Univariate models Multivariate model
N = 3361 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 70 (21%)

    3-3.4 Kg 166 (49%) 0.8 -0.6, 2.1 0.265 1.0 -0.6, 2.6 0.215
    ≥3.5 Kg 100 (30%) 0.9 -0.6, 2.3 0.246 1.5 -0.5, 3.5 0.149
Birth length






    <50 cm 123 (37%)

    50-51 cm 135 (40%) 0.2 -1.0, 1.3 0.783 -0.3 -1.7, 1.1 0.701
    ≥52 cm 77 (23%) 0.0 -1.4, 1.4 0.995 -0.6 -2.4, 1.3 0.560
Maternal education






    ≥5 years after graduation 191 (57%)

    <5 years after graduation 143 (43%) 0.1 -0.9, 1.2 0.777 -0.2 -1.2, 0.9 0.762
Maternal age at conception (years) 336 -0.1 -0.3, 0.0 0.049 -0.1 -0.3, 0.0 0.147
Maternal BMI before pregnancy






    <19 Kg/m2 47 (14%)

    19-23.9 Kg/m2 209 (62%) 0.1 -1.4, 1.7 0.856 0.4 -1.1, 1.9 0.622
    ≥24 Kg/m2 79 (24%) 0.6 -1.1, 2.3 0.489 0.5 -1.2, 2.3 0.572
Child sex






    Male 181 (54%)

    Female 155 (46%) 0.2 -0.9, 1.2 0.739 0.6 -0.5, 1.7 0.295
Maternal parity






    None 157 (47%)

    1 child or more 179 (53%) -1.2 -2.2, -0.2 0.022 -1.5 -2.7, -0.4 0.009
Breastfeeding duration






    Not breastfed 28 (8.5%)

    <24 weeks 114 (35%) -0.2 -2.2, 1.8 0.833 -0.1 -2.1, 1.9 0.952
    24-47 weeks 113 (34%) -0.3 -2.3, 1.7 0.803 0.1 -1.9, 2.2 0.887
    Still breastfeed at 48 weeks 73 (22%) 0.8 -1.3, 2.9 0.434 0.9 -1.1, 3.0 0.375
Gestational duration, completed weeks 336 0.2 -0.1, 0.5 0.229 0.1 -0.3, 0.5 0.648
Delivery mode






    Vaginal delivery 282 (84%)

    C-section 54 (16%) -0.2 -1.6, 1.2 0.805 -0.4 -1.9, 1.1 0.595
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 247 (80%)

    Between 6 and 12 months old 47 (15%) -0.1 -1.6, 1.5 0.946 -0.7 -2.3, 0.9 0.365
    Not introduced at 12 months old 13 (4.2%) -0.7 -3.4, 2.0 0.588 0.5 -2.4, 3.3 0.746
Presence of pets






    No 214 (72%)

    One or more 83 (28%) 0.3 -0.9, 1.5 0.589 0.3 -1.0, 1.6 0.648
Antibiotics use between 0-12 months old






    No 230 (69%)

    Yes 105 (31%) -0.7 -1.8, 0.4 0.220 -0.6 -1.8, 0.5 0.279
HOME questionnaire total score 302 -0.2 -0.4, 0.0 0.050 -0.2 -0.4, 0.0 0.096
Maternal anxiety and depression score during the third trimester of pregnancy 327 0.2 0.1, 0.3 <0.001 0.2 0.1, 0.4 <0.001
Maternal active smoking during pregnancy 18 (5.8%)





    No


    Yes
-0.1 -2.3, 2.1 0.926 -0.2 -2.8, 2.4 0.888
Child perinatal passive smoking up to one year 109 (33%)





    No


    Yes
1.2 0.1, 2.3 0.040 0.9 -0.3, 2.0 0.127
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 260 (82%)

    Other 57 (18%) -0.4 -1.8, 0.9 0.531 -0.5 -2.0, 0.9 0.473
Child age at the CBCL 2 years evaluation 336 0.1 -0.1, 0.3 0.292


Child age at the CBCL 2 years evaluation



0.1 -0.1, 0.3 0.365
No. Obs.



336





0.125

Adjusted R²



0.054

1 n (%); N
2 CI = Confidence Interval

Externe score Y2

Characteristic Univariate models Multivariate model
N = 3351 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 70 (21%)

    3-3.4 Kg 166 (50%) 0.0 -1.7, 1.8 0.981 -0.5 -2.7, 1.6 0.611
    ≥3.5 Kg 99 (30%) 0.5 -1.5, 2.4 0.630 -0.1 -2.8, 2.6 0.940
Birth length






    <50 cm 123 (37%)

    50-51 cm 134 (40%) 0.2 -1.3, 1.7 0.801 -0.3 -2.1, 1.6 0.789
    ≥52 cm 77 (23%) 0.6 -1.2, 2.4 0.545 0.1 -2.4, 2.6 0.917
Maternal education






    ≥5 years after graduation 191 (57%)

    <5 years after graduation 142 (43%) 1.2 -0.1, 2.6 0.078 0.7 -0.7, 2.1 0.304
Maternal age at conception (years) 335 -0.2 -0.3, 0.0 0.065 -0.2 -0.4, 0.0 0.053
Maternal BMI before pregnancy






    <19 Kg/m2 47 (14%)

    19-23.9 Kg/m2 209 (63%) 0.9 -1.1, 2.9 0.387 0.9 -1.1, 3.0 0.383
    ≥24 Kg/m2 78 (23%) 0.9 -1.4, 3.2 0.432 0.7 -1.6, 3.1 0.547
Child sex






    Male 180 (54%)

    Female 155 (46%) -0.9 -2.2, 0.5 0.217 -0.3 -1.8, 1.2 0.702
Maternal parity






    None 157 (47%)

    1 child or more 178 (53%) -0.1 -1.4, 1.3 0.930 -0.2 -1.7, 1.3 0.811
Breastfeeding duration






    Not breastfed 28 (8.6%)

    <24 weeks 113 (35%) -0.5 -3.1, 2.2 0.727 -0.1 -2.8, 2.6 0.941
    24-47 weeks 113 (35%) -0.8 -3.4, 1.8 0.556 0.1 -2.6, 2.8 0.942
    Still breastfeed at 48 weeks 73 (22%) 0.0 -2.8, 2.7 0.974 0.4 -2.4, 3.2 0.777
Gestational duration, completed weeks 335 0.1 -0.3, 0.6 0.557 0.1 -0.4, 0.6 0.663
Delivery mode






    Vaginal delivery 281 (84%)

    C-section 54 (16%) 0.1 -1.8, 1.9 0.939 -0.1 -2.1, 1.9 0.934
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 247 (80%)

    Between 6 and 12 months old 47 (15%) -0.4 -2.4, 1.6 0.701 -0.8 -2.8, 1.3 0.469
    Not introduced at 12 months old 13 (4.2%) 0.6 -2.9, 4.2 0.718 0.8 -3.0, 4.6 0.672
Presence of pets






    No 214 (72%)

    One or more 83 (28%) -0.9 -2.5, 0.7 0.273 -1.1 -2.7, 0.5 0.183
Antibiotics use between 0-12 months old






    No 229 (69%)

    Yes 105 (31%) 0.3 -1.2, 1.8 0.694 0.4 -1.1, 1.9 0.629
HOME questionnaire total score 301 -0.4 -0.6, -0.1 0.010 -0.3 -0.6, 0.0 0.044
Maternal anxiety and depression score during the third trimester of pregnancy 326 0.2 0.1, 0.3 0.005 0.2 0.1, 0.4 0.004
Maternal active smoking during pregnancy 18 (5.8%)





    No


    Yes
2.8 -0.3, 5.8 0.072 1.6 -1.4, 4.6 0.282
Child perinatal passive smoking up to one year 109 (33%)





    No


    Yes
1.6 0.2, 3.1 0.026 1.0 -0.5, 2.5 0.187
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 260 (82%)

    Other 57 (18%) -0.6 -2.4, 1.2 0.525 -0.6 -2.5, 1.3 0.555
Child age at the CBCL 2 years evaluation 335 0.0 -0.3, 0.2 0.795


Child age at the CBCL 2 years evaluation



0.0 -0.3, 0.2 0.878
No. Obs.



335





0.092

Adjusted R²



0.018

1 n (%); N
2 CI = Confidence Interval

SRS total score 3Y

Characteristic Univariate models Multivariate model
N = 3321 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 69 (21%)

    3-3.4 Kg 163 (49%) 1.2 -2.5, 4.8 0.523 1.6 -2.6, 5.7 0.462
    ≥3.5 Kg 100 (30%) 2.3 -1.7, 6.3 0.254 3.0 -2.3, 8.3 0.271
Birth length






    <50 cm 121 (37%)

    50-51 cm 132 (40%) -0.3 -3.5, 2.9 0.854 -1.1 -4.8, 2.5 0.534
    ≥52 cm 78 (24%) 1.1 -2.6, 4.8 0.557 -1.1 -6.0, 3.8 0.650
Maternal education






    ≥5 years after graduation 191 (58%)

    <5 years after graduation 139 (42%) 3.7 0.8, 6.5 0.011 4.0 1.2, 6.8 0.005
Maternal age at conception (years) 332 -0.3 -0.7, 0.1 0.105 -0.1 -0.5, 0.3 0.708
Maternal BMI before pregnancy






    <19 Kg/m2 46 (14%)

    19-23.9 Kg/m2 208 (63%) 1.2 -2.9, 5.4 0.561 2.0 -2.0, 6.0 0.325
    ≥24 Kg/m2 77 (23%) 1.3 -3.5, 6.0 0.599 1.7 -3.0, 6.3 0.474
Child sex






    Male 177 (53%)

    Female 155 (47%) -0.3 -3.1, 2.5 0.817 0.4 -2.4, 3.3 0.762
Maternal parity






    None 151 (45%)

    1 child or more 181 (55%) -4.7 -7.5, -2.0 <0.001 -6.5 -9.5, -3.6 <0.001
Breastfeeding duration






    Not breastfed 25 (7.7%)

    <24 weeks 113 (35%) -3.2 -8.9, 2.4 0.263 -2.0 -7.4, 3.5 0.474
    24-47 weeks 112 (35%) -3.9 -9.5, 1.8 0.182 -1.5 -7.0, 3.9 0.582
    Still breastfeed at 48 weeks 74 (23%) -4.4 -10.4, 1.5 0.143 -2.8 -8.5, 2.9 0.335
Gestational duration, completed weeks 332 0.6 -0.3, 1.5 0.188 0.4 -0.6, 1.4 0.388
Delivery mode






    Vaginal delivery 278 (84%)

    C-section 54 (16%) 1.1 -2.7, 4.8 0.583 -0.4 -4.2, 3.5 0.842
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 238 (79%)

    Between 6 and 12 months old 49 (16%) 0.6 -3.4, 4.5 0.784 -1.7 -5.8, 2.4 0.403
    Not introduced at 12 months old 15 (5.0%) 6.0 -0.8, 12.7 0.083 6.6 -0.3, 13.5 0.059
Presence of pets






    No 211 (72%)

    One or more 83 (28%) 0.1 -3.2, 3.4 0.944 -0.3 -3.9, 3.3 0.865
Antibiotics use between 0-12 months old






    No 228 (69%)

    Yes 103 (31%) -0.2 -3.2, 2.8 0.894 0.0 -3.0, 3.0 0.989
HOME questionnaire total score 303 -0.8 -1.3, -0.3 0.004 -0.7 -1.2, -0.1 0.018
Maternal anxiety and depression score during the third trimester of pregnancy 321 0.5 0.2, 0.8 <0.001 0.6 0.3, 1.0 <0.001
Maternal active smoking during pregnancy 19 (6.1%)





    No


    Yes
-1.0 -6.9, 4.9 0.737 -0.7 -7.0, 5.6 0.832
Child perinatal passive smoking up to one year 103 (32%)





    No


    Yes
-0.7 -3.7, 2.3 0.653 -1.7 -5.0, 1.5 0.300
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 257 (82%)

    Other 58 (18%) -1.4 -5.1, 2.3 0.456 -0.9 -4.8, 2.9 0.625
Child age at the SRS 3 years evaluation 332 0.3 0.0, 0.6 0.081


Child age at the SRS 3 years evaluation



0.2 -0.1, 0.5 0.280
No. Obs.



332





0.171

Adjusted R²



0.104

1 n (%); N
2 CI = Confidence Interval

BRIEF-P Y3

Inhibit score Y3

Characteristic Univariate models Multivariate model
N = 3301 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 68 (21%)

    3-3.4 Kg 161 (49%) 0.1 -1.4, 1.5 0.931 -0.5 -2.2, 1.3 0.607
    ≥3.5 Kg 101 (31%) 0.0 -1.6, 1.6 0.993 -1.2 -3.4, 1.0 0.297
Birth length






    <50 cm 118 (36%)

    50-51 cm 131 (40%) 0.8 -0.5, 2.1 0.230 1.1 -0.5, 2.6 0.171
    ≥52 cm 80 (24%) 1.3 -0.1, 2.8 0.074 2.0 0.0, 4.0 0.055
Maternal education






    ≥5 years after graduation 190 (58%)

    <5 years after graduation 138 (42%) 0.8 -0.3, 1.9 0.151 0.8 -0.4, 2.0 0.189
Maternal age at conception (years) 330 -0.1 -0.2, 0.0 0.191 -0.1 -0.2, 0.1 0.488
Maternal BMI before pregnancy






    <19 Kg/m2 46 (14%)

    19-23.9 Kg/m2 208 (63%) 0.9 -0.8, 2.5 0.309 0.8 -0.8, 2.5 0.321
    ≥24 Kg/m2 75 (23%) 0.7 -1.2, 2.6 0.493 0.6 -1.3, 2.6 0.536
Child sex






    Male 175 (53%)

    Female 155 (47%) -1.2 -2.3, 0.0 0.042 -0.7 -1.9, 0.5 0.237
Maternal parity






    None 148 (45%)

    1 child or more 182 (55%) -1.0 -2.1, 0.1 0.083 -1.5 -2.7, -0.2 0.021
Breastfeeding duration






    Not breastfed 24 (7.5%)

    <24 weeks 114 (35%) -0.3 -2.5, 2.0 0.813 0.1 -2.2, 2.4 0.936
    24-47 weeks 109 (34%) -0.3 -2.5, 2.0 0.829 0.6 -1.8, 3.0 0.627
    Still breastfeed at 48 weeks 75 (23%) 0.4 -2.0, 2.7 0.760 1.1 -1.3, 3.5 0.382
Gestational duration, completed weeks 330 0.0 -0.4, 0.3 0.790 -0.1 -0.5, 0.3 0.690
Delivery mode






    Vaginal delivery 276 (84%)

    C-section 54 (16%) 0.5 -1.0, 2.0 0.505 0.0 -1.6, 1.7 0.958
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 236 (79%)

    Between 6 and 12 months old 48 (16%) 0.1 -1.5, 1.7 0.933 -0.6 -2.3, 1.0 0.461
    Not introduced at 12 months old 15 (5.0%) 2.2 -0.4, 4.9 0.102 1.8 -1.0, 4.6 0.205
Presence of pets






    No 209 (72%)

    One or more 83 (28%) 0.3 -1.0, 1.6 0.625 0.1 -1.3, 1.6 0.878
Antibiotics use between 0-12 months old






    No 229 (70%)

    Yes 100 (30%) -0.2 -1.4, 1.0 0.793 0.0 -1.2, 1.3 0.958
HOME questionnaire total score 301 -0.1 -0.3, 0.1 0.442 -0.1 -0.3, 0.2 0.538
Maternal anxiety and depression score during the third trimester of pregnancy 320 0.1 0.0, 0.3 0.014 0.2 0.0, 0.3 0.017
Maternal active smoking during pregnancy 19 (6.2%)





    No


    Yes
0.5 -1.9, 2.9 0.680 -0.1 -2.7, 2.5 0.943
Child perinatal passive smoking up to one year 103 (32%)





    No


    Yes
0.5 -0.7, 1.7 0.411 0.3 -1.1, 1.7 0.667
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 255 (82%)

    Other 57 (18%) -0.6 -2.1, 0.9 0.449 -0.5 -2.1, 1.0 0.497
Child age at the SRS 3 years evaluation 330 0.1 0.0, 0.2 0.076


Child age at the SRS 3 years evaluation



0.1 0.0, 0.2 0.119
No. Obs.



330





0.097

Adjusted R²



0.022

1 n (%); N
2 CI = Confidence Interval

Shift score Y3

Characteristic Univariate models Multivariate model
N = 3381 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 70 (21%)

    3-3.4 Kg 166 (49%) 0.2 -0.7, 1.0 0.703 -0.2 -1.2, 0.8 0.736
    ≥3.5 Kg 102 (30%) 0.6 -0.3, 1.5 0.218 0.3 -1.0, 1.6 0.629
Birth length






    <50 cm 121 (36%)

    50-51 cm 135 (40%) 0.4 -0.4, 1.1 0.312 0.2 -0.6, 1.1 0.583
    ≥52 cm 81 (24%) 0.3 -0.5, 1.2 0.420 0.3 -0.9, 1.4 0.656
Maternal education






    ≥5 years after graduation 195 (58%)

    <5 years after graduation 141 (42%) 0.3 -0.4, 0.9 0.415 0.4 -0.3, 1.1 0.223
Maternal age at conception (years) 338 0.0 -0.1, 0.0 0.381 0.0 -0.1, 0.0 0.297
Maternal BMI before pregnancy






    <19 Kg/m2 46 (14%)

    19-23.9 Kg/m2 213 (63%) -0.5 -1.5, 0.4 0.257 -0.3 -1.3, 0.6 0.492
    ≥24 Kg/m2 78 (23%) -0.6 -1.7, 0.4 0.240 -0.6 -1.7, 0.5 0.251
Child sex






    Male 181 (54%)

    Female 157 (46%) 0.1 -0.5, 0.7 0.721 0.3 -0.4, 0.9 0.467
Maternal parity






    None 154 (46%)

    1 child or more 184 (54%) -0.5 -1.2, 0.1 0.099 -0.8 -1.5, -0.1 0.023
Breastfeeding duration






    Not breastfed 26 (7.9%)

    <24 weeks 115 (35%) 0.4 -0.9, 1.7 0.546 0.7 -0.5, 2.0 0.266
    24-47 weeks 112 (34%) 1.1 -0.2, 2.3 0.099 1.5 0.2, 2.8 0.021
    Still breastfeed at 48 weeks 77 (23%) 0.9 -0.4, 2.2 0.185 1.1 -0.2, 2.5 0.094
Gestational duration, completed weeks 338 0.1 -0.1, 0.3 0.357 0.1 -0.2, 0.3 0.562
Delivery mode






    Vaginal delivery 282 (83%)

    C-section 56 (17%) 0.2 -0.6, 1.1 0.577 0.2 -0.7, 1.1 0.608
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 243 (79%)

    Between 6 and 12 months old 49 (16%) 0.0 -0.9, 0.9 0.975 -0.6 -1.5, 0.3 0.205
    Not introduced at 12 months old 15 (4.9%) -0.1 -1.6, 1.4 0.902 0.0 -1.7, 1.7 0.998
Presence of pets






    No 215 (72%)

    One or more 84 (28%) -0.2 -1.0, 0.5 0.562 -0.4 -1.3, 0.4 0.326
Antibiotics use between 0-12 months old






    No 232 (69%)

    Yes 105 (31%) -0.1 -0.8, 0.6 0.756 -0.1 -0.8, 0.6 0.822
HOME questionnaire total score 309 0.0 -0.1, 0.1 0.688 0.0 -0.1, 0.1 0.983
Maternal anxiety and depression score during the third trimester of pregnancy 327 0.1 0.0, 0.2 0.014 0.1 0.0, 0.2 0.004
Maternal active smoking during pregnancy 19 (6.1%)





    No


    Yes
-0.6 -1.9, 0.7 0.348 -0.3 -2.7, 2.0 0.753
Child perinatal passive smoking up to one year 105 (32%)





    No


    Yes
0.0 -0.7, 0.7 0.996 -0.1 -0.9, 0.7 0.839
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 263 (82%)

    Other 57 (18%) 0.9 0.0, 1.7 0.045 1.0 0.1, 1.9 0.027
Child age at the SRS 3 years evaluation 338 0.0 0.0, 0.1 0.324


Child age at the SRS 3 years evaluation



0.0 0.0, 0.1 0.308
No. Obs.



338





0.098

Adjusted R²



0.026

1 n (%); N
2 CI = Confidence Interval

BRIEF-P emotional control score Y3

Characteristic Univariate models Multivariate model
N = 3371 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 70 (21%)

    3-3.4 Kg 165 (49%) 0.2 -0.8, 1.2 0.707 0.0 -1.2, 1.1 0.945
    ≥3.5 Kg 102 (30%) 0.4 -0.7, 1.4 0.506 0.2 -1.3, 1.7 0.817
Birth length






    <50 cm 121 (36%)

    50-51 cm 134 (40%) 0.3 -0.6, 1.1 0.525 0.2 -0.8, 1.2 0.706
    ≥52 cm 81 (24%) 0.4 -0.6, 1.3 0.463 0.3 -1.0, 1.7 0.632
Maternal education






    ≥5 years after graduation 194 (58%)

    <5 years after graduation 141 (42%) 0.4 -0.4, 1.1 0.300 0.4 -0.4, 1.2 0.283
Maternal age at conception (years) 337 -0.1 -0.2, 0.0 0.048 -0.1 -0.2, 0.0 0.166
Maternal BMI before pregnancy






    <19 Kg/m2 46 (14%)

    19-23.9 Kg/m2 212 (63%) 0.5 -0.6, 1.6 0.381 0.7 -0.4, 1.8 0.211
    ≥24 Kg/m2 78 (23%) 0.2 -1.1, 1.5 0.746 0.3 -1.0, 1.6 0.699
Child sex






    Male 180 (53%)

    Female 157 (47%) 0.0 -0.8, 0.7 0.925 0.2 -0.6, 1.0 0.636
Maternal parity






    None 153 (45%)

    1 child or more 184 (55%) -0.9 -1.6, -0.2 0.016 -1.2 -2.0, -0.3 0.007
Breastfeeding duration






    Not breastfed 26 (7.9%)

    <24 weeks 115 (35%) -0.1 -1.6, 1.3 0.846 0.1 -1.4, 1.6 0.927
    24-47 weeks 111 (34%) 0.5 -1.0, 2.0 0.493 1.0 -0.6, 2.5 0.217
    Still breastfeed at 48 weeks 77 (23%) 0.7 -0.9, 2.2 0.379 1.0 -0.6, 2.6 0.218
Gestational duration, completed weeks 337 0.1 -0.1, 0.3 0.475 0.1 -0.2, 0.3 0.675
Delivery mode






    Vaginal delivery 282 (84%)

    C-section 55 (16%) 0.2 -0.8, 1.2 0.767 0.0 -1.0, 1.1 0.945
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 243 (79%)

    Between 6 and 12 months old 48 (16%) -0.1 -1.2, 0.9 0.786 -0.4 -1.6, 0.7 0.476
    Not introduced at 12 months old 15 (4.9%) 1.1 -0.7, 2.9 0.236 1.3 -0.6, 3.2 0.175
Presence of pets






    No 215 (72%)

    One or more 84 (28%) 0.4 -0.4, 1.3 0.305 0.2 -0.8, 1.1 0.746
Antibiotics use between 0-12 months old






    No 232 (69%)

    Yes 104 (31%) -0.1 -0.9, 0.7 0.835 0.1 -0.8, 0.9 0.849
HOME questionnaire total score 308 -0.1 -0.2, 0.1 0.440 0.0 -0.2, 0.1 0.633
Maternal anxiety and depression score during the third trimester of pregnancy 327 0.1 0.0, 0.2 0.037 0.1 0.0, 0.2 0.008
Maternal active smoking during pregnancy 19 (6.1%)





    No


    Yes
0.0 -1.6, 1.6 0.997 0.1 -2.0, 2.3 0.893
Child perinatal passive smoking up to one year 105 (32%)





    No


    Yes
0.3 -0.5, 1.1 0.455 0.1 -0.8, 0.9 0.850
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 262 (82%)

    Other 57 (18%) 0.0 -1.0, 1.0 0.979 0.1 -0.9, 1.2 0.809
Child age at the SRS 3 years evaluation 337 0.0 -0.1, 0.1 0.923


Child age at the SRS 3 years evaluation



0.0 -0.1, 0.1 0.802
No. Obs.



337





0.087

Adjusted R²



0.013

1 n (%); N
2 CI = Confidence Interval

BRIEF-P working memory score Y3

Characteristic Univariate models Multivariate model
N = 3291 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 69 (21%)

    3-3.4 Kg 162 (49%) -1.0 -2.2, 0.2 0.114 -1.4 -2.9, 0.1 0.061
    ≥3.5 Kg 98 (30%) -0.5 -1.8, 0.8 0.468 -0.7 -2.6, 1.1 0.437
Birth length






    <50 cm 118 (36%)

    50-51 cm 131 (40%) -0.1 -1.2, 1.0 0.848 -0.2 -1.5, 1.0 0.720
    ≥52 cm 79 (24%) -0.2 -1.4, 1.1 0.808 -0.5 -2.2, 1.2 0.568
Maternal education






    ≥5 years after graduation 192 (59%)

    <5 years after graduation 135 (41%) 0.8 -0.1, 1.8 0.085 0.9 0.0, 1.9 0.061
Maternal age at conception (years) 329 0.0 -0.2, 0.1 0.553 0.0 -0.1, 0.1 0.865
Maternal BMI before pregnancy






    <19 Kg/m2 45 (14%)

    19-23.9 Kg/m2 207 (63%) 0.7 -0.7, 2.1 0.341 0.9 -0.5, 2.4 0.192
    ≥24 Kg/m2 76 (23%) -0.3 -1.9, 1.3 0.705 -0.1 -1.7, 1.5 0.915
Child sex






    Male 177 (54%)

    Female 152 (46%) -0.1 -1.0, 0.9 0.908 -0.2 -1.2, 0.8 0.738
Maternal parity






    None 152 (46%)

    1 child or more 177 (54%) -1.2 -2.1, -0.3 0.012 -1.4 -2.4, -0.3 0.009
Breastfeeding duration






    Not breastfed 25 (7.8%)

    <24 weeks 113 (35%) 0.5 -1.5, 2.4 0.643 0.7 -1.2, 2.7 0.460
    24-47 weeks 110 (34%) 0.5 -1.4, 2.5 0.580 1.3 -0.7, 3.2 0.203
    Still breastfeed at 48 weeks 73 (23%) 0.5 -1.5, 2.5 0.626 1.2 -0.8, 3.2 0.232
Gestational duration, completed weeks 329 0.1 -0.2, 0.4 0.352 0.3 -0.1, 0.6 0.112
Delivery mode






    Vaginal delivery 274 (83%)

    C-section 55 (17%) 0.2 -1.1, 1.4 0.780 -0.2 -1.5, 1.1 0.781
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 235 (79%)

    Between 6 and 12 months old 49 (16%) -0.3 -1.7, 1.0 0.626 -0.9 -2.2, 0.4 0.171
    Not introduced at 12 months old 14 (4.7%) 1.4 -0.9, 3.7 0.237 1.4 -1.2, 4.1 0.291
Presence of pets






    No 208 (72%)

    One or more 82 (28%) -0.8 -1.8, 0.3 0.159 -0.9 -2.0, 0.2 0.128
Antibiotics use between 0-12 months old






    No 224 (68%)

    Yes 104 (32%) 0.2 -0.8, 1.2 0.728 0.4 -0.6, 1.5 0.418
HOME questionnaire total score 300 -0.2 -0.4, 0.0 0.062 -0.1 -0.3, 0.1 0.211
Maternal anxiety and depression score during the third trimester of pregnancy 318 0.1 0.0, 0.2 0.102 0.1 0.0, 0.2 0.015
Maternal active smoking during pregnancy 18 (5.9%)





    No


    Yes
0.6 -1.4, 2.6 0.556 -0.3 -2.6, 2.1 0.806
Child perinatal passive smoking up to one year 103 (32%)





    No


    Yes
1.2 0.2, 2.1 0.024 0.9 -0.4, 2.1 0.177
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 256 (82%)

    Other 55 (18%) -1.3 -2.6, 0.0 0.045 -0.8 -2.1, 0.6 0.263
Child age at the SRS 3 years evaluation 329 0.1 0.0, 0.2 0.234


Child age at the SRS 3 years evaluation



0.1 0.0, 0.2 0.232
No. Obs.



329





0.124

Adjusted R²



0.052

1 n (%); N
2 CI = Confidence Interval

BRIEF-P plan/organization score Y3

Characteristic Univariate models Multivariate model
N = 3351 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 70 (21%)

    3-3.4 Kg 165 (49%) -0.2 -0.9, 0.6 0.678 -0.3 -1.2, 0.6 0.536
    ≥3.5 Kg 100 (30%) -0.1 -0.9, 0.8 0.893 -0.2 -1.4, 1.0 0.728
Birth length






    <50 cm 121 (36%)

    50-51 cm 135 (40%) -0.1 -0.8, 0.6 0.745 -0.2 -1.1, 0.6 0.557
    ≥52 cm 78 (23%) 0.2 -0.6, 1.0 0.567 0.2 -0.9, 1.3 0.767
Maternal education






    ≥5 years after graduation 193 (58%)

    <5 years after graduation 140 (42%) 0.8 0.2, 1.4 0.008 0.9 0.3, 1.6 0.003
Maternal age at conception (years) 335 0.0 -0.1, 0.0 0.209 0.0 -0.1, 0.1 0.470
Maternal BMI before pregnancy






    <19 Kg/m2 46 (14%)

    19-23.9 Kg/m2 212 (63%) 0.0 -0.9, 0.9 0.950 0.0 -0.9, 0.9 0.938
    ≥24 Kg/m2 76 (23%) -0.2 -1.3, 0.8 0.663 -0.3 -1.3, 0.8 0.613
Child sex






    Male 179 (53%)

    Female 156 (47%) -0.2 -0.8, 0.4 0.416 -0.2 -0.8, 0.5 0.558
Maternal parity






    None 153 (46%)

    1 child or more 182 (54%) -0.5 -1.1, 0.1 0.086 -0.7 -1.3, 0.0 0.050
Breastfeeding duration






    Not breastfed 26 (8.0%)

    <24 weeks 114 (35%) -0.4 -1.6, 0.8 0.509 -0.2 -1.4, 1.0 0.719
    24-47 weeks 111 (34%) 0.2 -1.0, 1.3 0.797 0.6 -0.7, 1.9 0.369
    Still breastfeed at 48 weeks 76 (23%) -0.1 -1.4, 1.1 0.838 0.3 -1.0, 1.6 0.651
Gestational duration, completed weeks 335 0.0 -0.2, 0.2 0.841 0.1 -0.2, 0.3 0.603
Delivery mode






    Vaginal delivery 281 (84%)

    C-section 54 (16%) 0.1 -0.7, 1.0 0.733 -0.1 -1.0, 0.8 0.804
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 241 (79%)

    Between 6 and 12 months old 49 (16%) 0.0 -0.9, 0.9 0.977 -0.4 -1.3, 0.5 0.351
    Not introduced at 12 months old 15 (4.9%) 1.6 0.1, 3.0 0.037 1.6 0.1, 3.1 0.040
Presence of pets






    No 213 (72%)

    One or more 84 (28%) -0.3 -1.0, 0.4 0.368 -0.5 -1.2, 0.2 0.184
Antibiotics use between 0-12 months old






    No 232 (69%)

    Yes 102 (31%) 0.1 -0.5, 0.8 0.727 0.2 -0.5, 0.8 0.614
HOME questionnaire total score 306 0.0 -0.1, 0.1 0.769 0.1 -0.1, 0.2 0.402
Maternal anxiety and depression score during the third trimester of pregnancy 324 0.1 0.0, 0.1 0.042 0.1 0.0, 0.2 0.013
Maternal active smoking during pregnancy 19 (6.1%)





    No


    Yes
-0.1 -1.4, 1.2 0.922 -0.4 -1.8, 0.9 0.539
Child perinatal passive smoking up to one year 103 (32%)





    No


    Yes
0.5 -0.2, 1.1 0.159 0.4 -0.3, 1.2 0.255
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 261 (82%)

    Other 57 (18%) -0.3 -1.1, 0.5 0.466 -0.2 -1.1, 0.6 0.592
Child age at the SRS 3 years evaluation 335 0.0 0.0, 0.1 0.208


Child age at the SRS 3 years evaluation



0.0 0.0, 0.1 0.311
No. Obs.



335





0.107

Adjusted R²



0.035

1 n (%); N
2 CI = Confidence Interval

IQ Y3

IQ verbal comprehension score Y3

Characteristic Univariate models Multivariate model
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 63 (20%)

    3-3.4 Kg 159 (50%) -0.7 -4.1, 2.7 0.697 1.9 -2.1, 5.9 0.357
    ≥3.5 Kg 93 (30%) -0.9 -4.7, 2.8 0.619 2.1 -3.1, 7.3 0.421
Birth length






    <50 cm 116 (37%)

    50-51 cm 124 (39%) -2.0 -4.9, 1.0 0.191 -2.1 -5.6, 1.4 0.249
    ≥52 cm 74 (24%) -1.1 -4.5, 2.2 0.504 -0.4 -5.0, 4.2 0.868
Maternal education






    ≥5 years after graduation 182 (58%)

    <5 years after graduation 131 (42%) -2.1 -4.7, 0.5 0.105 -1.5 -4.2, 1.1 0.255
Maternal age at conception (years) 315 0.0 -0.4, 0.3 0.907 0.1 -0.3, 0.4 0.655
Maternal BMI before pregnancy






    <19 Kg/m2 45 (14%)

    19-23.9 Kg/m2 198 (63%) 0.7 -3.0, 4.5 0.709 0.8 -3.0, 4.6 0.678
    ≥24 Kg/m2 71 (23%) 0.9 -3.4, 5.2 0.690 1.1 -3.3, 5.5 0.621
Child sex






    Male 167 (53%)

    Female 148 (47%) 2.6 0.0, 5.1 0.046 1.5 -1.3, 4.2 0.293
Maternal parity






    None 139 (44%)

    1 child or more 176 (56%) -3.3 -5.8, -0.7 0.012 -3.0 -5.8, -0.2 0.036
Breastfeeding duration






    Not breastfed 25 (8.1%)

    <24 weeks 102 (33%) 0.7 -4.3, 5.8 0.779 -0.7 -5.8, 4.5 0.802
    24-47 weeks 108 (35%) 2.4 -2.7, 7.4 0.353 1.0 -4.1, 6.1 0.692
    Still breastfeed at 48 weeks 72 (23%) 4.3 -1.0, 9.5 0.112 4.3 -1.1, 9.6 0.117
Gestational duration, completed weeks 315 -0.3 -1.2, 0.5 0.451 -0.4 -1.4, 0.6 0.418
Delivery mode






    Vaginal delivery 263 (83%)

    C-section 52 (17%) -0.2 -3.7, 3.2 0.887 -1.2 -4.8, 2.4 0.507
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 232 (80%)

    Between 6 and 12 months old 45 (16%) 1.0 -2.7, 4.7 0.593 1.3 -2.7, 5.3 0.514
    Not introduced at 12 months old 13 (4.5%) -7.6 -14.0, -1.2 0.021 -6.0 -12.5, 0.5 0.069
Presence of pets






    No 203 (73%)

    One or more 77 (28%) 0.3 -2.7, 3.3 0.850 0.5 -2.8, 3.7 0.779
Antibiotics use between 0-12 months old






    No 212 (68%)

    Yes 102 (32%) -0.8 -3.6, 1.9 0.546 -0.7 -3.5, 2.1 0.631
HOME questionnaire total score 309 0.8 0.3, 1.2 0.002 0.6 0.1, 1.1 0.021
Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.2 -0.5, 0.1 0.176 -0.1 -0.4, 0.2 0.335
Maternal active smoking during pregnancy 19 (6.5%)





    No


    Yes
-0.7 -6.1, 4.8 0.807 1.3 -4.9, 7.5 0.681
Child perinatal passive smoking up to one year 100 (33%)





    No


    Yes
-1.2 -3.9, 1.6 0.407 -0.5 -3.5, 2.6 0.763
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 246 (82%)

    Other 53 (18%) -3.0 -6.4, 0.4 0.081 -2.6 -6.3, 1.1 0.166
Child age at the IQ 3 years evaluation 315 0.3 0.0, 0.6 0.065


Child age at the IQ 3 years evaluation



0.3 0.0, 0.6 0.082
No. Obs.



315





0.124

Adjusted R²



0.048

1 n (%); N
2 CI = Confidence Interval

IQ visuospacial score Y3

Characteristic Univariate models Multivariate model
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 63 (20%)

    3-3.4 Kg 159 (50%) 1.3 -2.0, 4.5 0.452 0.6 -3.4, 4.6 0.786
    ≥3.5 Kg 93 (30%) 0.9 -2.7, 4.5 0.611 0.0 -5.1, 5.1 0.990
Birth length






    <50 cm 116 (37%)

    50-51 cm 124 (39%) 0.9 -1.9, 3.8 0.511 0.4 -3.0, 3.9 0.808
    ≥52 cm 74 (24%) 0.3 -2.9, 3.6 0.839 0.3 -4.2, 4.9 0.883
Maternal education






    ≥5 years after graduation 182 (58%)

    <5 years after graduation 131 (42%) 0.6 -1.9, 3.1 0.630 1.2 -1.4, 3.8 0.363
Maternal age at conception (years) 315 0.2 -0.2, 0.5 0.349 0.1 -0.3, 0.4 0.649
Maternal BMI before pregnancy






    <19 Kg/m2 45 (14%)

    19-23.9 Kg/m2 198 (63%) 0.9 -2.7, 4.5 0.622 0.5 -3.2, 4.3 0.772
    ≥24 Kg/m2 71 (23%) 1.7 -2.5, 5.9 0.429 1.6 -2.7, 6.0 0.464
Child sex






    Male 167 (53%)

    Female 148 (47%) 0.5 -2.0, 2.9 0.708 0.1 -2.6, 2.9 0.934
Maternal parity






    None 139 (44%)

    1 child or more 176 (56%) 2.6 0.1, 5.0 0.041 2.4 -0.4, 5.2 0.089
Breastfeeding duration






    Not breastfed 25 (8.1%)

    <24 weeks 102 (33%) 3.6 -1.2, 8.4 0.138 3.3 -1.7, 8.3 0.200
    24-47 weeks 108 (35%) 5.3 0.5, 10.0 0.030 5.1 0.0, 10.1 0.048
    Still breastfeed at 48 weeks 72 (23%) 6.1 1.1, 11.1 0.016 6.7 1.5, 11.9 0.011
Gestational duration, completed weeks 315 0.0 -0.8, 0.8 0.948 0.0 -1.0, 1.0 0.982
Delivery mode






    Vaginal delivery 263 (83%)

    C-section 52 (17%) -2.3 -5.6, 1.1 0.182 -2.4 -6.0, 1.1 0.176
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 232 (80%)

    Between 6 and 12 months old 45 (16%) -0.8 -4.4, 2.9 0.672 -0.4 -3.8, 3.1 0.840
    Not introduced at 12 months old 13 (4.5%) -3.0 -9.3, 3.4 0.357 -2.2 -8.8, 4.3 0.501
Presence of pets






    No 203 (73%)

    One or more 77 (28%) -1.4 -4.4, 1.5 0.339 -1.6 -4.7, 1.4 0.297
Antibiotics use between 0-12 months old






    No 212 (68%)

    Yes 102 (32%) 1.6 -1.0, 4.2 0.225 1.7 -1.2, 4.5 0.248
HOME questionnaire total score 309 0.3 -0.2, 0.7 0.274 0.4 -0.2, 0.9 0.171
Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.1 -0.3, 0.2 0.707 0.0 -0.3, 0.3 0.853
Maternal active smoking during pregnancy 19 (6.5%)





    No


    Yes
-2.0 -7.2, 3.2 0.453 -1.6 -7.0, 3.7 0.552
Child perinatal passive smoking up to one year 100 (33%)





    No


    Yes
-0.9 -3.6, 1.8 0.522 -0.6 -3.5, 2.3 0.678
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 246 (82%)

    Other 53 (18%) -1.8 -5.2, 1.5 0.286 -3.4 -6.9, 0.1 0.058
Child age at the IQ 3 years evaluation 315 0.0 -0.3, 0.3 0.862


Child age at the IQ 3 years evaluation



0.0 -0.3, 0.3 0.939
No. Obs.



315





0.078

Adjusted R²






1 n (%); N
2 CI = Confidence Interval

IQ work memory score Y3

Characteristic Univariate models Multivariate model
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 63 (20%)

    3-3.4 Kg 159 (50%) 0.8 -2.4, 4.1 0.610 0.3 -3.6, 4.3 0.875
    ≥3.5 Kg 93 (30%) -1.4 -4.9, 2.1 0.441 -2.2 -7.2, 2.8 0.390
Birth length






    <50 cm 116 (37%)

    50-51 cm 124 (39%) 0.0 -2.9, 2.8 0.973 0.3 -3.1, 3.7 0.846
    ≥52 cm 74 (24%) -1.3 -4.6, 1.9 0.415 0.0 -4.5, 4.5 0.998
Maternal education






    ≥5 years after graduation 182 (58%)

    <5 years after graduation 131 (42%) 0.0 -2.5, 2.5 0.974 0.2 -2.4, 2.8 0.886
Maternal age at conception (years) 315 -0.1 -0.5, 0.2 0.362 -0.2 -0.6, 0.1 0.239
Maternal BMI before pregnancy






    <19 Kg/m2 45 (14%)

    19-23.9 Kg/m2 198 (63%) -2.1 -5.7, 1.4 0.240 -3.0 -6.7, 0.7 0.111
    ≥24 Kg/m2 71 (23%) -1.1 -5.2, 3.0 0.597 -1.6 -5.8, 2.7 0.477
Child sex






    Male 167 (53%)

    Female 148 (47%) 1.7 -0.7, 4.2 0.169 1.3 -1.4, 4.0 0.353
Maternal parity






    None 139 (44%)

    1 child or more 176 (56%) 1.7 -0.7, 4.2 0.167 2.9 0.2, 5.7 0.036
Breastfeeding duration






    Not breastfed 25 (8.1%)

    <24 weeks 102 (33%) 0.7 -4.1, 5.5 0.779 0.8 -4.3, 5.8 0.767
    24-47 weeks 108 (35%) 0.1 -4.7, 4.9 0.970 -0.6 -5.6, 4.3 0.804
    Still breastfeed at 48 weeks 72 (23%) 4.0 -1.0, 9.0 0.117 4.2 -1.0, 9.3 0.112
Gestational duration, completed weeks 315 0.0 -0.8, 0.8 0.970 0.2 -0.8, 1.1 0.731
Delivery mode






    Vaginal delivery 263 (83%)

    C-section 52 (17%) -1.3 -4.6, 2.0 0.447 -0.5 -3.9, 3.0 0.795
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 232 (80%)

    Between 6 and 12 months old 45 (16%) -1.7 -5.2, 1.8 0.349 -0.5 -4.0, 3.0 0.775
    Not introduced at 12 months old 13 (4.5%) -4.2 -10.3, 1.9 0.176 -3.7 -10.3, 2.9 0.269
Presence of pets






    No 203 (73%)

    One or more 77 (28%) -0.8 -3.7, 2.1 0.600 -0.7 -3.8, 2.3 0.636
Antibiotics use between 0-12 months old






    No 212 (68%)

    Yes 102 (32%) 0.9 -1.7, 3.5 0.506 1.0 -1.8, 3.8 0.469
HOME questionnaire total score 309 0.2 -0.2, 0.7 0.328 0.3 -0.2, 0.8 0.220
Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.1 -0.4, 0.1 0.279 -0.1 -0.4, 0.2 0.360
Maternal active smoking during pregnancy 19 (6.5%)





    No


    Yes
-4.8 -9.9, 0.3 0.062 -3.8 -9.3, 1.6 0.166
Child perinatal passive smoking up to one year 100 (33%)





    No


    Yes
-1.0 -3.6, 1.7 0.468 0.2 -2.7, 3.1 0.910
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 246 (82%)

    Other 53 (18%) -1.6 -4.9, 1.6 0.326 -2.8 -6.3, 0.7 0.117
Child age at the IQ 3 years evaluation 315 0.1 -0.2, 0.4 0.493


Child age at the IQ 3 years evaluation



0.1 -0.2, 0.4 0.665
No. Obs.



315





0.088

Adjusted R²



0.008

1 n (%); N
2 CI = Confidence Interval

IQ total score Y3

Characteristic Univariate models Multivariate model
N = 3151 Beta 95% CI2 p-value Beta 95% CI2 p-value
Birth weight






    <3 Kg 63 (20%)

    3-3.4 Kg 159 (50%) 0.5 -2.8, 3.8 0.781 1.2 -2.8, 5.2 0.552
    ≥3.5 Kg 93 (30%) -0.3 -4.0, 3.3 0.854 0.3 -4.8, 5.5 0.896
Birth length






    <50 cm 116 (37%)

    50-51 cm 124 (39%) -0.3 -3.1, 2.6 0.858 -0.2 -3.7, 3.2 0.888
    ≥52 cm 74 (24%) -0.6 -3.9, 2.7 0.731 0.4 -4.2, 5.0 0.861
Maternal education






    ≥5 years after graduation 182 (58%)

    <5 years after graduation 131 (42%) -0.1 -2.6, 2.5 0.951 0.7 -2.0, 3.3 0.606
Maternal age at conception (years) 315 0.0 -0.3, 0.4 0.805 0.0 -0.3, 0.4 0.829
Maternal BMI before pregnancy






    <19 Kg/m2 45 (14%)

    19-23.9 Kg/m2 198 (63%) 0.5 -3.1, 4.2 0.779 0.0 -3.7, 3.8 0.991
    ≥24 Kg/m2 71 (23%) 1.3 -3.0, 5.5 0.560 1.0 -3.3, 5.4 0.643
Child sex






    Male 167 (53%)

    Female 148 (47%) 2.1 -0.4, 4.6 0.099 1.4 -1.4, 4.1 0.319
Maternal parity






    None 139 (44%)

    1 child or more 176 (56%) 0.3 -2.2, 2.8 0.799 0.8 -2.0, 3.6 0.583
Breastfeeding duration






    Not breastfed 25 (8.1%)

    <24 weeks 102 (33%) 2.3 -2.6, 7.3 0.358 1.6 -3.4, 6.7 0.526
    24-47 weeks 108 (35%) 3.8 -1.1, 8.7 0.129 3.0 -2.0, 8.1 0.235
    Still breastfeed at 48 weeks 72 (23%) 5.9 0.7, 11.0 0.026 6.3 1.1, 11.6 0.018
Gestational duration, completed weeks 315 -0.2 -1.0, 0.7 0.703 -0.2 -1.2, 0.8 0.661
Delivery mode






    Vaginal delivery 263 (83%)

    C-section 52 (17%) -1.6 -5.0, 1.7 0.343 -1.8 -5.3, 1.7 0.316
Period of introduction of solid food 0-12 months old






    Between 0 and 6 months old 232 (80%)

    Between 6 and 12 months old 45 (16%) -0.4 -4.0, 3.2 0.845 0.3 -3.3, 4.0 0.861
    Not introduced at 12 months old 13 (4.5%) -6.9 -13.2, -0.6 0.031 -5.4 -12.2, 1.4 0.120
Presence of pets






    No 203 (73%)

    One or more 77 (28%) -0.9 -3.8, 2.1 0.566 -0.8 -4.0, 2.3 0.597
Antibiotics use between 0-12 months old






    No 212 (68%)

    Yes 102 (32%) 0.5 -2.1, 3.2 0.691 0.7 -2.1, 3.5 0.637
HOME questionnaire total score 309 0.6 0.2, 1.1 0.009 0.6 0.1, 1.1 0.017
Maternal anxiety and depression score during the third trimester of pregnancy 306 -0.2 -0.5, 0.1 0.187 -0.1 -0.5, 0.2 0.364
Maternal active smoking during pregnancy 19 (6.5%)





    No


    Yes
-3.0 -8.3, 2.2 0.257 -1.8 -7.2, 3.6 0.522
Child perinatal passive smoking up to one year 100 (33%)





    No


    Yes
-1.3 -4.0, 1.5 0.362 -0.5 -3.4, 2.4 0.731
Main mode of child care at 12 months (2 categories, optimized 2)






    Collective day care 246 (82%)

    Other 53 (18%) -3.1 -6.5, 0.2 0.068 -4.2 -7.8, -0.7 0.020
Child age at the IQ 3 years evaluation 315 0.1 -0.1, 0.4 0.323


Child age at the IQ 3 years evaluation



0.1 -0.2, 0.4 0.499
No. Obs.



315





0.099

Adjusted R²



0.020

1 n (%); N
2 CI = Confidence Interval

Sensitivity analyses - rarefaction threshold

CBCL Y2

Interne score Y2

Characteristic Child CBCL interne score at 2 years
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 332 0.01 -0.01, 0.03 0.536
Specific richness (threshold 5000 reads, n=339) 321 0.01 -0.01, 0.03 0.485
Specific richness (threshold 10000 reads, n=339) 321 0.01 -0.01, 0.03 0.237
Shannon diversity (threshold 5000 reads, n=350, main analysis) 332 0.38 -0.56, 1.33 0.424
Shannon diversity (threshold 5000 reads, n=339) 321 0.46 -0.50, 1.41 0.348
Shannon diversity (threshold 10000 reads, n=339) 321 0.46 -0.49, 1.42 0.343
1 CI = Confidence Interval

Externe score Y2

Characteristic Child CBCL externe score at 2 years
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 331 -0.01 -0.03, 0.02 0.629
Specific richness (threshold 5000 reads, n=339) 320 -0.01 -0.03, 0.02 0.611
Specific richness (threshold 10000 reads, n=339) 320 0.00 -0.02, 0.02 0.908
Shannon diversity (threshold 5000 reads, n=350, main analysis) 331 0.50 -0.76, 1.75 0.436
Shannon diversity (threshold 5000 reads, n=339) 320 0.47 -0.82, 1.75 0.475
Shannon diversity (threshold 10000 reads, n=339) 320 0.47 -0.81, 1.75 0.470
1 CI = Confidence Interval

SRS total score 3Y

Characteristic Child SRS total score at 3 years
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 327 0.02 -0.04, 0.07 0.570
Specific richness (threshold 5000 reads, n=339) 316 0.02 -0.04, 0.07 0.512
Specific richness (threshold 10000 reads, n=339) 316 0.01 -0.03, 0.06 0.549
Shannon diversity (threshold 5000 reads, n=350, main analysis) 327 -0.10 -2.58, 2.38 0.938
Shannon diversity (threshold 5000 reads, n=339) 316 0.05 -2.47, 2.57 0.968
Shannon diversity (threshold 10000 reads, n=339) 316 0.05 -2.47, 2.57 0.970
1 CI = Confidence Interval

BRIEF-P Y3

Inhibit score Y3

Characteristic Child inhibition score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 325 0.00 -0.02, 0.03 0.711
Specific richness (threshold 5000 reads, n=339) 314 0.01 -0.02, 0.03 0.637
Specific richness (threshold 10000 reads, n=339) 314 0.00 -0.02, 0.02 0.813
Shannon diversity (threshold 5000 reads, n=350, main analysis) 325 0.07 -0.97, 1.11 0.894
Shannon diversity (threshold 5000 reads, n=339) 314 0.22 -0.84, 1.28 0.687
Shannon diversity (threshold 10000 reads, n=339) 314 0.21 -0.85, 1.27 0.693
1 CI = Confidence Interval

Shift score Y3

Characteristic Child shift score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 333 0.00 -0.01, 0.01 0.766
Specific richness (threshold 5000 reads, n=339) 322 0.00 -0.01, 0.01 0.729
Specific richness (threshold 10000 reads, n=339) 322 0.00 -0.01, 0.01 0.531
Shannon diversity (threshold 5000 reads, n=350, main analysis) 333 -0.16 -0.75, 0.42 0.587
Shannon diversity (threshold 5000 reads, n=339) 322 -0.08 -0.68, 0.51 0.783
Shannon diversity (threshold 10000 reads, n=339) 322 -0.08 -0.67, 0.51 0.784
1 CI = Confidence Interval

BRIEF-P emotional control score Y3

Characteristic Child emotional control score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 332 0.01 0.00, 0.03 0.090
Specific richness (threshold 5000 reads, n=339) 321 0.01 0.00, 0.03 0.082
Specific richness (threshold 10000 reads, n=339) 321 0.01 0.00, 0.02 0.109
Shannon diversity (threshold 5000 reads, n=350, main analysis) 332 0.53 -0.16, 1.22 0.130
Shannon diversity (threshold 5000 reads, n=339) 321 0.59 -0.11, 1.28 0.097
Shannon diversity (threshold 10000 reads, n=339) 321 0.59 -0.11, 1.28 0.097
1 CI = Confidence Interval

BRIEF-P working memory score Y3

Characteristic Child working memory score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 324 0.01 -0.01, 0.03 0.430
Specific richness (threshold 5000 reads, n=339) 315 0.01 -0.01, 0.03 0.409
Specific richness (threshold 10000 reads, n=339) 315 0.00 -0.01, 0.02 0.532
Shannon diversity (threshold 5000 reads, n=350, main analysis) 324 0.05 -0.83, 0.92 0.915
Shannon diversity (threshold 5000 reads, n=339) 315 0.09 -0.79, 0.98 0.839
Shannon diversity (threshold 10000 reads, n=339) 315 0.09 -0.79, 0.97 0.843
1 CI = Confidence Interval

BRIEF-P plan/organization score Y3

Characteristic Child plan/organization score at 3 years (BRIEF-P)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 330 0.01 0.00, 0.02 0.149
Specific richness (threshold 5000 reads, n=339) 319 0.01 0.00, 0.02 0.104
Specific richness (threshold 10000 reads, n=339) 319 0.01 0.00, 0.02 0.135
Shannon diversity (threshold 5000 reads, n=350, main analysis) 330 0.19 -0.37, 0.74 0.508
Shannon diversity (threshold 5000 reads, n=339) 319 0.20 -0.35, 0.76 0.469
Shannon diversity (threshold 10000 reads, n=339) 319 0.20 -0.35, 0.76 0.470
1 CI = Confidence Interval

IQ Y3

IQ verbal comprehension score Y3

Characteristic Child verbal comprehension score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 310 -0.01 -0.06, 0.04 0.690
Specific richness (threshold 5000 reads, n=339) 301 -0.01 -0.06, 0.04 0.663
Specific richness (threshold 10000 reads, n=339) 301 -0.01 -0.05, 0.03 0.675
Shannon diversity (threshold 5000 reads, n=350, main analysis) 310 -1.28 -3.66, 1.10 0.290
Shannon diversity (threshold 5000 reads, n=339) 301 -1.18 -3.59, 1.23 0.336
Shannon diversity (threshold 10000 reads, n=339) 301 -1.19 -3.59, 1.22 0.333
1 CI = Confidence Interval

IQ visuospacial score Y3

Characteristic Child visuospatiale score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 310 0.00 -0.05, 0.05 0.922
Specific richness (threshold 5000 reads, n=339) 301 0.00 -0.05, 0.04 0.867
Specific richness (threshold 10000 reads, n=339) 301 0.00 -0.04, 0.04 0.973
Shannon diversity (threshold 5000 reads, n=350, main analysis) 310 0.35 -1.99, 2.69 0.768
Shannon diversity (threshold 5000 reads, n=339) 301 0.24 -2.09, 2.58 0.837
Shannon diversity (threshold 10000 reads, n=339) 301 0.25 -2.08, 2.57 0.835
1 CI = Confidence Interval

IQ work memory score Y3

Characteristic Child work memory score at 3 years (IQ test)
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 310 -0.01 -0.05, 0.04 0.800
Specific richness (threshold 5000 reads, n=339) 301 -0.01 -0.05, 0.04 0.827
Specific richness (threshold 10000 reads, n=339) 301 0.00 -0.04, 0.04 0.902
Shannon diversity (threshold 5000 reads, n=350, main analysis) 310 -1.04 -3.34, 1.25 0.372
Shannon diversity (threshold 5000 reads, n=339) 301 -1.08 -3.36, 1.20 0.352
Shannon diversity (threshold 10000 reads, n=339) 301 -1.07 -3.35, 1.20 0.353
1 CI = Confidence Interval

IQ total score Y3

Characteristic Child total IQ score at 3 years
N Beta 95% CI1 p-value
Specific richness (threshold 5000 reads, n=350, main analysis) 310 0.00 -0.05, 0.05 0.997
Specific richness (threshold 5000 reads, n=339) 301 0.00 -0.05, 0.05 0.949
Specific richness (threshold 10000 reads, n=339) 301 0.00 -0.04, 0.04 0.998
Shannon diversity (threshold 5000 reads, n=350, main analysis) 310 -0.64 -3.00, 1.71 0.590
Shannon diversity (threshold 5000 reads, n=339) 301 -0.67 -3.02, 1.69 0.578
Shannon diversity (threshold 10000 reads, n=339) 301 -0.67 -3.02, 1.68 0.576
1 CI = Confidence Interval

Sensitivity analysis - effect of HOME variable

CBCL Y2

Interne score Y2

Characteristic Child CBCL interne score at 2 years adjusted for HOME variable at 3 years (main analysis) Child CBCL interne score at 2 years not adjusted for HOME variable at 3 years
N Beta 95% CI1 p-value N Beta 95% CI1 p-value
Specific richness 332 0.01 -0.01, 0.03 0.536 332 0.01 -0.01, 0.03 0.437
Shannon diversity 332 0.38 -0.56, 1.33 0.424 332 0.45 -0.49, 1.39 0.348
Phylum Firmicutes 336 0.00 -0.03, 0.02 0.842 336 0.00 -0.03, 0.02 0.952
Phylum Actinobacteria 336 0.02 -0.01, 0.04 0.151 336 0.02 -0.01, 0.04 0.168
Phylum Bacteroidetes 336 0.00 -0.03, 0.03 0.869 336 0.00 -0.03, 0.03 0.836
Phylum Proteobacteria 336 -0.03 -0.06, 0.00 0.080 336 -0.03 -0.06, 0.00 0.068
Genus Bifidobacterium 336 0.02 -0.01, 0.04 0.134 336 0.02 -0.01, 0.04 0.151
Genus Bacteroides 336 -0.02 -0.05, 0.02 0.323 336 -0.02 -0.05, 0.01 0.302
Genus Blautia 336 -0.04 -0.09, 0.01 0.131 336 -0.04 -0.09, 0.02 0.177
Genera Escherichia and Shigella 336 -0.02 -0.06, 0.01 0.210 336 -0.03 -0.06, 0.01 0.172
1 CI = Confidence Interval

Externe score Y2

Characteristic Child CBCL externe score at 2 years adjusted for HOME variable at 3 years (main analysis) Child CBCL externe score at 2 years not adjusted for HOME variable at 3 years
N Beta 95% CI1 p-value N Beta 95% CI1 p-value
Specific richness 331 -0.01 -0.03, 0.02 0.629 331 0.00 -0.03, 0.02 0.786
Shannon diversity 331 0.50 -0.76, 1.75 0.436 331 0.61 -0.65, 1.86 0.341
Phylum Firmicutes 335 0.02 -0.01, 0.06 0.156 335 0.03 -0.01, 0.06 0.114
Phylum Actinobacteria 335 0.02 -0.01, 0.05 0.232 335 0.02 -0.01, 0.05 0.266
Phylum Bacteroidetes 335 -0.01 -0.05, 0.03 0.547 335 -0.01 -0.05, 0.03 0.520
Phylum Proteobacteria 335 -0.05 -0.10, -0.01 0.024 335 -0.05 -0.10, -0.01 0.019
Genus Bifidobacterium 335 0.02 -0.01, 0.05 0.203 335 0.02 -0.01, 0.05 0.237
Genus Bacteroides 335 -0.02 -0.06, 0.02 0.396 335 -0.02 -0.06, 0.02 0.374
Genus Blautia 335 0.03 -0.04, 0.10 0.377 335 0.04 -0.03, 0.11 0.287
Genera Escherichia and Shigella 335 -0.04 -0.09, 0.01 0.158 335 -0.04 -0.09, 0.01 0.119
1 CI = Confidence Interval